scholarly journals Changing patterns in clinical–histological presentation and renal outcome over the last five decades in a cohort of 499 patients with lupus nephritis

2018 ◽  
Vol 77 (9) ◽  
pp. 1318-1325 ◽  
Author(s):  
Gabriella Moroni ◽  
Paolo Gilles Vercelloni ◽  
Silvana Quaglini ◽  
Mariele Gatto ◽  
Davide Gianfreda ◽  
...  

ObjectivesTo evaluate changes in demographic, clinical and histological presentation, and prognosis of lupus nephritis (LN) over time.Patients and methodsWe studied a multicentre cohort of 499 patients diagnosed with LN from 1970 to 2016. The 46-year follow-up was subdivided into three periods (P): P1 1970–1985, P2 1986–2001 and P3 2002–2016, and patients accordingly grouped based on the year of LN diagnosis. Predictors of patient and renal survival were investigated by univariate and multivariate proportional hazards Cox regression analyses. Survival curves were compared using the log-rank test.ResultsA progressive increase in patient age at the time of LN diagnosis (p<0.0001) and a longer time between systemic lupus erythematosus onset and LN occurrence (p<0.0001) was observed from 1970 to 2016. During the same period, the frequency of renal insufficiency at the time of LN presentation progressively decreased (p<0.0001) and that of isolated urinary abnormalities increased (p<0.0001). No changes in histological class and activity index were observed, while chronicity index significantly decreased from 1970 to 2016 (p=0.023). Survival without end-stage renal disease (ESRD) was 87% in P1, 94% in P2% and 99% in P3 at 10 years, 80% in P1 and 90% in P2 at 20 years (p=0.0019). At multivariate analysis, male gender, arterial hypertension, absence of maintenance immunosuppressive therapy, increased serum creatinine, and high activity and chronicity index were independent predictors of ESRD.ConclusionsClinical presentation of LN has become less severe in the last years, leading to a better long-term renal survival.

Lupus ◽  
2018 ◽  
Vol 27 (11) ◽  
pp. 1838-1846 ◽  
Author(s):  
J Nossent ◽  
W Raymond ◽  
A Kang ◽  
D Wong ◽  
M Ognjenovic ◽  
...  

Objectives To investigate the current demographic, clinical and histological characteristics of patients with lupus nephritis (LN) in Western Australia (WA) with regards to their predictive value for patient and renal outcome. Methods Retrospective study of adult systemic lupus erythematosus (SLE) patients with a first renal biopsy demonstrating LN between 1997 and 2017 at a metropolitan tertiary hospital in WA. Clinical data were collected at baseline and last follow-up with renal biopsy findings classified by International Society of Nephrology (ISN) criteria. Annual incidence rates (AIRs)/100,000, Kaplan–Meyer curves and Cox regression hazard ratio for independent predictors for patient and renal survival were applied. Results The AIR was 3.3, 3.1 and 0.4 for Asian ( n = 29), Indigenous Australian (IA) ( n = 11) and Caucasian ( n = 43) patients, respectively ( p < 0.01). There was no significant subgroup difference regarding ISN class (proliferative 66%, membranous 19%, mesangial 15%), levels of proteinuria (median PCR 300 mg/mmol) or frequency of raised creatinine (31%), anti-dsDNA antibody (89%) or hypocomplementaemia (88%). Treatment included corticosteroids (91%), cyclophosphamide (30%), mycophenolate (67%) and antihypertensive drugs (67%). Five- (81%) and 10-year (70%) survival was lower for IAs than for Caucasians and Asians (95% each at both time points) ( p = 0.016). Five- and 10-year renal survival (endpoint renal replacement therapy (RRT)) was 86% and 64% for IA vs 100% for Asian, 100% and 96% for Caucasian patients ( p = 0.02). IA background was the only independent predictor for poor patient survival and together with male gender also for renal survival. Only 25% of all patients remained free of any organ damage with non-renal damage observed in 53% of survivors. Conclusions LN incidence in WA was 0.75/100,000 with the lowest rate observed in Caucasians. While Asian patients have the same favourable outlook as Caucasians, the outcome is much bleaker for IA patients. Other clinical and histological findings did not predict outcomes, and importantly more than half of all surviving patients accrued non-renal damage.


2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Ryosuke Umeda ◽  
Soshiro Ogata ◽  
Shigeo Hara ◽  
Kazuo Takahashi ◽  
Daijo Inaguma ◽  
...  

Abstract Background Although the 2018 revised International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification was proposed recently, until now, no reports have been made comparing the association of renal prognosis between the 2018 revised ISN/RPS classification and the 2003 ISN/RPS classification. The present study aimed to assess the usefulness, especially of activity and chronicity assessment, of the 2018 revised ISN/RPS classification for lupus nephritis (LN) in terms of renal prognosis compared to the classification in 2003. Methods We retrospectively collected medical records of 170 LN patients from the database of renal biopsy at Fujita Health University from January 2003 to April 2019. Each renal biopsy specimen was reevaluated according to both the 2003 ISN/RPS classification and the 2018 revised ISN/RPS classification. Renal endpoint was defined as a 30% decline of estimated glomerular filtration rate (eGFR). Results A total of 129 patients were class III/IV±V (class III, 44 patients; class IV, 35 patients; class III/IV+V, 50 patients). The mean age was 42 years, 88% were female, and the median observation period was 50.5 months. Renal prognosis was significantly different among the classes and significantly poor in the patients with higher modified National Institute of Health (mNIH) chronicity index (C index, ≥ 4) by a log-rank test (p = 0.05 and p = 0.02, respectively). By Cox proportional hazard models, only the C index was significantly associated with renal outcome (hazard ratio 1.32, 95% CI 1.11–1.56, p ≤ 0.01), while the classes, the 2003 activity and chronicity subdivision, and the mNIH activity index had no significant association with renal outcome. Each component of the C index was significantly associated with renal outcome in different models. Conclusion This study demonstrates that the 2018 revised ISN/RPS classification was more useful in terms of association with renal prognosis compared to the 2003 ISN/RPS classification.


2020 ◽  
Author(s):  
Ryosuke Umeda ◽  
Soshiro Ogata ◽  
Shigeo Hara ◽  
Kazuo Takahashi ◽  
Daijo Inaguma ◽  
...  

Abstract Background: Although 2018 revised ISN/RPS classification was proposed recently, until now, no reports have been made comparing the association of renal prognosis between 2018 revised ISN/RPS classification and 2003 ISN/RPS classification. The present study aimed to assess the usefulness, especially of activity and chronicity assessment, of the 2018 revised International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification for lupus nephritis (LN) in terms of renal prognosis compared to the classification in 2003.Methods: We retrospectively collected medical records of 170 LN patients from the database of renal biopsy in Fujita Health University from January 2003 to April 2019. Each renal biopsy specimen was reevaluated according to both the 2003 ISN/RPS classification and the 2018 revised ISN/RPS classification. Renal endpoint was defined as 30% decline of estimated glomerular filtration rate (eGFR). Results: A total 129 patients were class III/IV±V (class III, 44 patients; class IV, 35 patients; class III/IV+V, 50 patients). Mean age was 42 years, 88% were female, and median observation period was 50.5 months. Renal prognosis was significantly different among the classes, and significantly poor in the patients with higher modified National Institute of Health (mNIH) Chronicity index (C index, ≥4) by a log-rank test (p=0.05, p=0.02 respectively). By Cox proportional hazard models, only C index was significantly associated with renal outcome (Hazard Ratio; 1.32, 95% CI; 1.11-1.56, p≤0.01), while the classes, the 2003 activity and chronicity subdivision, and mNIH activity index had no significant association with renal outcome. Each component of C index was significantly associated with renal outcome in different models. Conclusion: This study demonstrates that the 2018 revised ISN/RPS classification was more useful in terms of association with renal prognosis compared to the 2003 ISN/RPS classification


2019 ◽  
Vol 46 (8) ◽  
pp. 912-919 ◽  
Author(s):  
Si-Jia Shao ◽  
Jin-Hua Hou ◽  
Guo-Tong Xie ◽  
Wen Sun ◽  
Dan-Dan Liang ◽  
...  

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.


2020 ◽  
Vol 79 (8) ◽  
pp. 1077-1083 ◽  
Author(s):  
Gabriella Moroni ◽  
Mariele Gatto ◽  
Francesco Tamborini ◽  
Silvana Quaglini ◽  
Francesca Radice ◽  
...  

ObjectivesShort-term predictive endpoints of chronic kidney disease (CKD) are needed in lupus nephritis (LN). We tested response to therapy at 1 year.MethodsWe considered patients with LN who underwent renal biopsy followed by induction therapy between January 1970 and December 2016. LN was assessed using the International Society of Nephrology/Renal Pathology Society (2003) criteria and the National Institute of Health (NIH) activity and chronicity index. The renal outcome was CKD. Response was defined according to EULAR/European League Against Rheumatism/European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations: complete: proteinuria <0.5 g/24 hours, (near) normal estimated glomerular filtration rate (eGFR); partial: ≥50% proteinuria reduction to subnephrotic levels, (near) normal eGFR; and no response: all the other cases. Logistic regression analysis was employed for 12-month response and Cox regression for CKD prediction.ResultsWe studied 381 patients (90.5% Caucasians). After 12-month therapy, 58%, 26% and 16% of patients achieved complete, partial and no response, respectively, according to EULAR/ERA-EDTA. During a median follow-up of 10.7 (IQR: 4.97–18.80) years, 53 patients developed CKD. At 15 years, CKD-free survival rate was 95.2%, 87.6% and 55.4% in patients with complete, partial and no response at 12 months, respectively (p<0.0001). CKD-free survival rates did not differ between complete and partial responders (p=0.067). Serum creatinine (HR: 1.485, 95% CI 1.276 to 1.625), eGFR (HR 0.967, 95% CI 0.957 to 0.977) and proteinuria at 12 months (HR 1.234, 95% CI 1.111 to 1.379) were associated with CKD, yet no reliable cut-offs were identified on the receiver operating characteristic curve. In multivariable analysis, no EULAR/ERA-EDTA response at 12 months (HR 5.165, 95% CI 2.770 to 7.628), low C4 (HR 1.053, 95% CI 1.019 to 1.089) and persistent arterial hypertension (HR 3.154, 95% CI 1.500 to 4.547) independently predicted CKD.ConclusionsLack of EULAR/ERA-EDTA response at 12 months predicts CKD.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Asaka Hachiya ◽  
Munetoshi Karasawa ◽  
Takahiro Imaizumi ◽  
Noritoshi Kato ◽  
Takayuki Katsuno ◽  
...  

AbstractLupus nephritis (LN) is a life-threatening complication of systemic lupus erythematosus. The 2003 pathological classification of LN was revised in 2016; it quantitatively evaluates the interstitium in addition to the glomeruli. We performed a retrospective multi-centre cohort study and investigated the utility of the 2016 classification—including the activity index (AI), chronicity index (CI), and each pathological component to predict complete remission or renal function decline, defined as 1.5-fold increase in serum creatinine levels—and compare with that of the 2003 classification. Ninety-one consecutive adult patients with first-onset class III/IV LN who were newly prescribed any immunosuppressants were enrolled and followed up for a median of 51 months from January 2004. Cox regression analysis demonstrated the subclasses based on the 2003 classification, which mainly evaluate glomerular lesions, were not associated with clinical outcomes. After adjustments for estimated glomerular filtration rate and urinary protein levels, higher CI and higher interstitial fibrosis and lower hyaline deposit scores were associated with renal functional decline. Similarly, higher CI and interstitial inflammation scores were associated with failure to achieve complete remission. Therefore, the 2016 classification can predict the clinical outcomes more precisely than the 2003 classification.


2020 ◽  
Vol 9 (2) ◽  
pp. e14-e14
Author(s):  
Eman Hassan Abdelbary ◽  
Noha Farouk Ahmed ◽  
Adel Abdelmohsen Ghorab

Introduction: Lupus nephritis (LN) is a substantial manifestation of systemic lupus erythematosus (SLE). HDAC6 is overexpressed in various kidney diseases, and its inhibition slows kidney injury progression. Urinary TFF3 increases in chronic kidney diseases (CKDs) and may be associated with patient’s outcome. Objectives: This study aimed to examine the relationship between renal HDAC6 and TFF3 proteins expression and with clinicopathologic characteristics and outcome of LN. Patients and Methods: HDAC6 and TFF3 proteins’ expression was immunohistochemically detected in 56 cases of LN. They were correlated to patients’ age, gender, urinary 24 hours protein and serum creatinine levels at baseline and during follow up. Additionally, they were correlated to LN classes, activity index (AI) and chronicity index (CI) and relapse free survival (RFS). Results: HDAC6 overexpression was significantly associated with serum creatinine and 24 hours proteinuria levels at baseline (P = 0.041 and P =0.026 respectively) and during follow up (P < 0.001). It was associated with AI and CI of class III and IV LN (P = 0.047 and 0.003 respectively). TFF3 overexpression was associated with higher serum creatinine and more proteinuria at baseline (P = 0.015 and 0.001 respectively) and during follow up (P < 0.001). It was significantly associated with higher CI (P = 0.001). Both markers were associated with shorter RFS (P < 0.001). Conclusion: HDAC6 and TFF3 proteins are associated with clinicopathologic features of renal damage in LN. They are reliable predictors of patients’ RFS, which makes them good candidates for risk stratification of patients and targeted therapy.


2020 ◽  
Vol 20 (01) ◽  
pp. 9-20
Author(s):  
Roy Tsz Chung Ho ◽  
Moon Ho Leung

Objective: To identify the clinical factors associated with renal response and flare in lupus nephritis (LN). Methods: All 115 patients with biopsy-proven LN diagnosed between January 2002 and June 2015 in a tertiary centre comprised of an inception cohort that was followed up until February 2017. Baseline demographic, clinical parameters, renal biopsy histology, induction and maintenance immunosuppressive therapies, complete renal response (CRR), creatinine doubling, end-stage renal disease (ESRD), renal flares and infections were retrieved and analyzed with univariate log-rank test and multivariate Cox regression. Results: At the time of the first renal biopsy, the age of patients was 38 ± 12.2 years (mean ± standard deviation), 90% female and systemic lupus erythematosus (SLE) disease duration 46 months (median); 67.0% were LN class IV or class IV + V. Patients were followed up for 104 ±49 months after biopsy. At months 3, 6, 12 and 24, a cumulative 25%, 46%, 66% and 76% of patients had achieved CRR, respectively. However, 49.5% who had CRR experienced [Formula: see text]1 infection of renal flare, with cumulative risk of 5%, 17%, 25% and 43% at year 1, 2, 3 and 5, respectively. Multivariate analysis showed that nephrotic syndrome ([Formula: see text] = 0.03) and delay of renal biopsy [Formula: see text]2 months from the onset of LN ([Formula: see text] ¡ 0.01) were negatively associated with CRR. Hydroxychloroquine use was beneficial in attaining CRR ([Formula: see text] = 0.03, hazard ratio = 1.70, 95% CI: 1.04, 2.80) and preventing renal flare ([Formula: see text] = 0.01, odds ratio = 0.51, 95% CI: 0.29, 0.88). By the end of the study, 80% of patients remained in CRR though 10.4% patients ended up in ESRD (all class IV), 8.7% died and 28.7% had [Formula: see text]1 infection episode requiring hospitalization. Conclusion: Most LN patients could achieve CRR after immunosuppressive therapy but renal flares were common over time. Infective complications were fairly frequent but the incidence of ESRD was low. The use of hydroxychloroquine was associated with better renal response and fewer flares.


Lupus ◽  
2019 ◽  
Vol 28 (5) ◽  
pp. 658-666
Author(s):  
Y M Chen ◽  
W T Hung ◽  
Y W Liao ◽  
C Y Hsu ◽  
T Y Hsieh ◽  
...  

Lupus nephritis (LN) is the leading cause of mortality in lupus patients. This study aimed to investigate the treatment outcome and renal histological risk factors of LN in a tertiary referral center. Between 2006 and 2017, a retrospective observational study enrolled 148 biopsy-proven LN patients. After propensity score matching, 75 cases were included for further analysis. The classification and scoring of LN were assessed according to the International Society of Nephrology/Renal Pathology Society. Treatment response was evaluated by daily urine protein and urinalysis at two years after commencing induction treatment and the development of end-stage renal disease (ESRD). In total, 50.7% patients achieved complete remission (CR) or partial remission (PR), while 49.3% patients were categorized as nonresponders. Therapeutic responses in terms of CR/PR rates were associated with Systemic Lupus Erythematosus Disease Activity Index scores (odds ratio (OR): 1.34, 95% confidence interval (CI): 1.12–1.60, p = 0.001). Moreover, higher baseline creatinine levels (hazard ratio (HR): 2.10, 95% CI: 1.29–3.40, p = 0.003), higher renal activity index (HR: 1.30, 95% CI: 1.07–1.58, p = 0.008) and chronicity index (HR: 1.40, 95% CI: 1.06–1.85, p = 0.017) predicted ESRD. Among pathological scores, cellular crescents (HR: 4.42, 95% CI: 1.01–19.38, p = 0.049) and fibrous crescents (HR: 5.93, 95% CI: 1.41–24.92, p = 0.015) were independent risk factors for ESRD. In conclusion, higher lupus activity was a good prognostic marker for renal remission. Renal histology was predictive of ESRD. Large-scale prospective studies are required to verify the efficacy of mycophenolate in combination with azathioprine or cyclosporine in LN patients.


2019 ◽  
Vol 46 (11) ◽  
pp. 1478-1484 ◽  
Author(s):  
Chao Li ◽  
Desmond Y.H. Yap ◽  
Gavin Chan ◽  
Yu-bing Wen ◽  
Hang Li ◽  
...  

Objective.Renal thrombotic microangiopathy (TMA) is an uncommon pathological finding in lupus nephritis (LN), and its clinical significance remains to be defined.Methods.Twenty-four patients with lupus nephritis (LN) and renal TMA were selected from a retrospective review of 677 biopsy-proven LN patients, and compared with 48 LN controls without TMA (1:2 ratio) matched according to demographics and treatments.Results.Renal TMA was noted in 3.5% of kidney biopsies of LN. TMA was associated with a higher prevalence of anti-Ro (45.8% vs 18.8%; p = 0.016), higher Systemic Lupus Erythematosus Disease Activity Index scores (21.4 ± 8.5 vs 10.8 ± 2.3; p < 0.001), lower estimated glomerular filtration rate (eGFR; 16.8 ± 11.7 ml/min vs 77.8 ± 28.6 ml/min; p < 0.001), and a higher percentage of patients who required dialysis (37.5% vs 2.1%; p < 0.001) at the time of kidney biopsy. Activity and chronicity indices [median (range)] were higher in the TMA group [11 (2–19) and 3 (1–8), respectively, compared with 7 (0–15) and 1 (0–3) in controls; p = 0.004 and p < 0.001; respectively]. Patients with TMA showed inferior 5-year renal survival and higher incidence of chronic kidney disease at last followup (70% and 66.6%, respectively, compared with 95% and 29.2% in controls; p = 0.023 and 0.002, respectively). The TMA group also showed lower median eGFR compared with controls [50.1 (IQR 7–132) ml/min vs 85.0 (IQR 12–147) ml/min; p = 0.003]. Five-year patient survival rate was similar between the 2 groups (87% and 98% in TMA and control group, respectively; p = 0.127).Conclusion.TMA in kidney biopsy was associated with more severe clinical and histological activity, and significantly inferior longterm renal outcome in LN.


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