Lupus Nephritis Class Research Articles

Immune gene expression and functional networks in distinct lupus nephritis classes

ObjectiveTo explore the utility of the NanoString platform in elucidating kidney immune transcripts for class III, IV and V lupus nephritis (LN) using a retrospective cohort of formalin-fixed paraffin-embedded (FFPE)...

Beyond ISN/RPS Lupus Nephritis Classification: Adding Chronicity Index to Clinical Variables Predicts Kidney Survival.

A renewed interest for activity and chronicity indices as predictors of lupus nephritis (LN) outcome has emerged. Revised National Institutes of Health activity and chronicity indices have been proposed to classify LN lesions, but they should be validated by future studies. The aims of this study were (1) to detect the histologic features associated with the development of kidney function impairment (KFI), and (2) to identify the best clinical-histologic model to predict KFI at time of kidney biopsy. Patients with LN who had more than ten glomeruli per kidney biopsy specimen were admitted to the study. Univariate and multivariate logistic regression and Cox proportional hazards models were used to investigate whether activity and chronicity indices could predict KFI development. Among 203 participants with LN followed for 14 years, correlations were found between the activity index, and its components, and clinical-laboratory signs of active LN at baseline. The chronicity index was correlated with serum creatinine. Thus, serum creatinine was significantly and directly correlated with both activity and chronicity indices. In the multivariate analysis, glomerulosclerosis (OR, 3.05; 95% CI, 1.17 to 7.91; P=0.02) and fibrous crescents (OR, 6.84; 95% CI, 3.22 to 14.52; P<0.001) associated with either moderate/severe tubular atrophy (OR, 3.17; 95% CI, 1.04 to 9.64; P=0.04), or with interstitial fibrosis (OR, 2.36; 95% CI, 1.05 to 5.32; P=0.04), predicted KFI. Considering both clinical and histologic features, serum creatinine (OR, 1.68; 95% CI, 1.31 to 2.15; P<0.001), arterial hypertension (OR, 4.64; 95% CI, 1.90 to 11.32; P<0.001), glomerulosclerosis (OR, 2.12; 95% CI, 1.00 to 4.50; P=0.05), and fibrous crescents (OR, 5.18; 95% CI, 2.43 to 11.04; P<0.001) independently predicted KFI. Older age (P<0.001) and longer delay between clinical onset of LN and kidney biopsy (P<0.001) were significantly correlated with baseline chronicity index. The chronicity index and its components, but not the activity index, were significantly associated with an impairment of kidney function. The Cox model showed that serum creatinine, arterial hypertension, chronic glomerular lesions, and delay in kidney biopsy predicted KFI. These data reinforce the importance of timely kidney biopsy in LN.

Urinary Sediments as Predictors of the Histopathology of Lupus Nephritis.

Lupus nephritis (LN) is a major risk factor for morbidity and mortality in systemic lupus erythematosus (SLE). Urinalysis has an invaluable role in the diagnosis of various renal and urological diseases. Examinations of the urinary sediment using phase contrast microscopy (PCM) may add more information to help earlier diagnoses of LN. This cross-sectional study aimed to assess the possible role of the components of urinary sediment examined using PCM in discriminating the proliferative classes of LN (III and IV ± V) from the non-proliferative classes (I, II, and V), and to detect the correlation between the components of urinary sediment and indices of both activity and chronicity found by the renal biopsy. The study was conducted on 40 SLE patients for whom a renal biopsy was indicated. Clinical, demographic, and laboratory data and the results of the histopathological renal biopsy were collected. The morning before the renal biopsy; urine samples were collected from every patient and examined by PCM. Receiver operating characteristic curves were used to detect the area under the curve to predict proliferative LN. The correlations of counts of leukocytes, erythrocytes, all dysmorphic erythrocytes, acanthocytes, and stomatocytes with the indices of activity and chronicity were significant (activity: P = 0.027, P = 0.015, P = 0.033, P = 0.040, and P <0.001*; chronicity: P = 0.035, P = 0.009, P = 0.027, P = 0.010, and P <0.001, respectively). For patients with SLE, urinary sediment examinations can suggest a renal biopsy for the histopathology of LN.

Clinicopathological Study of Males with Lupus Nephritis: Pathologist's Experience at a Tertiary-Care Center.

Background:Systemic lupus erythematosus (SLE) is an autoimmune systemic disorder, more common in females of reproductive age-group as compared with males. There are very few studies regarding lupus nephritis (LN) in males. Hence, we decided to study the clinical and pathological findings of LN in males.Materials and Methods:We carried out a retrospective study over a period of 5 years (January 2014–December 2018) on indicated native renal biopsies from male patients with LN. We analyzed the clinical, laboratory, and histological findings of these patients.Results:Renal biopsies were performed on 228 patients with LN, of which 29 (12.72%) biopsies were in male patients. The mean age at presentation was 28.3 ± 12.98 years. Edema (65.5%) was the most common clinical feature followed by arthritis (27.58%), fever (27.58%), and skin rash (24.1%). The mean values for 24 hours urinary protein, serum double-stranded DNA, serum antinuclear antibody, and serum complement C3 were 4.98 ± 2.91 g, 137.7 ± 91.93 IU/mL, 2.96 ± 1.78, and 65.07 ± 36.30 mg/dL, respectively. On histology, the most common class of LN was Class IV (34.48%) followed by Class V (20.68%), combined Class IV + V (20.68%), Classes II, III, and III + V.Conclusion:LN can affect males, although the prevalence is lower than in females. The incidence of LN in our study was 12.7% with the most common histological class being diffuse proliferative LN.

An Analysis of the Correlation Between Clinical Indexes and Pathological Classifications in 202 Patients with Lupus Nephritis

ObjectiveTo investigate the correlation between clinical indexes and pathological classifications in 202 patients with lupus nephritis (LN).MethodsA total of 202 LN cases were retrospectively analyzed. All these patients met the four diagnostic criteria for systemic lupus erythematosus (SLE) of the American College of Rheumatology revised in 1997. The pathological diagnostic criteria of LN were in accordance with the pathological LN classification revised by the International Society of Nephrology and the Society of Kidney Pathology in 2003. The patients were scored according to the improved SLE Disease Activity Index 2000 (SLEDAI-2K), and their basic data, clinical data, laboratory data, and pathological data were collected.ResultsAmong the 202 patients, the ratio of male to female was 1:5.73, and type IV was the most common pathological LN classification. There were differences in the urine analysis, hypertension incidence, blood cell analysis, blood lipids, renal function, plasma albumin, immunological indexes, renal pathological score among the different pathological types (P < 0.05). In the early finding of renal function damage of the patients, cystatin C sensitivity was significantly higher than that of serum creatinine and blood urea nitrogen. Multiple linear regression analysis show that there are strong correlations between AI and SLEDAI, 24hU-Pr, serum C3, serum ALB, BUN, creatinine, UA and PLT (P < 0.001); and there are correlations between AI and serum IgM, IgA, C4, TC and LDL-C (P < 0.05).ConclusionThere is a clear correlation between pathological classifications and clinical indexes of LN.Trial RegistrationShen-PJ-2018-40, Study on Clinical and Molecular Mechanism of SLE.

High Systemic Type I Interferon Activity Is Associated With Active Class III/IV Lupus Nephritis.

Previous studies suggest a link between high serum type I interferon (IFN) and lupus nephritis (LN). We determined whether serum IFN activity is associated with subtypes of LN and studied renal tissues and cells to understand the effect of IFN in LN. Two hundred and twenty-one patients with systemic lupus erythematosus were studied. Serum IFN activity was measured by WISH bioassay. mRNA in situ hybridization was used in renal tissue to measure expression of the representative IFN-induced gene, IFN-induced protein with tetratricopeptide repeats-1 (IFIT1), and the plasmacytoid dendritic cell (pDC) marker gene C-type lectin domain family-4 member C (CLEC4C). Podocyte cell line gene expression was measured by real-time PCR. Class III/IV LN prevalence was significantly increased in patients with high serum IFN compared with those with low IFN (odds ratio 5.40, P = 0.009). In multivariate regression models, type I IFN was a stronger predictor of class III/IV LN than complement C3 or anti-dsDNA antibody, and could account for the association of these variables with LN. IFIT1 expression was increased in all classes of LN, but most in the glomerular areas of active class III/IV LN kidneys. IFIT1 expression was not closely colocalized with pDCs. IFN directly activated podocyte cell lines to induce chemokines and proapoptotic molecules. Systemic high IFN is involved in the pathogenesis of severe LN. We did not find colocalization of pDCs with IFN signature in renal tissue, and instead observed the greatest intensity of the IFN signature in glomerular areas, which could suggest a blood source of IFN.

O004. Assessment of the impact of lupus nephritis on clinical, biological parameters, disease activity and mortality in pediatric Systemic Lupus Erythematosus

Abstract Background Systemic lupus erythematosus (SLE) is an autoimmune disorder affecting multiple organ systems. Kidney involvement is one of the most frequent and severe manifestations of pediatric systemic lupus erythematosus (pSLE), seriously affecting the prognosis. It usually manifests as glomerulonephritis of varying severity. Objective: Knowledge of the correlation of lupus nephritis (LN) with clinical, biological, immunological parameters, disease activity and mortality in pediatric systemic lupus erythematosus is limited. This study aims to describe the impact of renal involvement with these different determinants. Methods This was a prospective, multicenter, descriptive 36-month study (January 2015 - December 2018) including patients less than 16 years of age with LN. The presence of LN was defined according to the American College of Rheumatology classification SLE criteria. The LN class was determined by renal biopsy and was classified according to the Morphology in Kidney International Society of Nephrology (ISN)/Renal Pathology Society (RPS) 2004 classification of lupus nephritis. The disease activity was estimated by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), the use of which has been validated in children. Means, percentages and Chi-square tests were specified. P values less than 0.05 were considered statistically significant. Results We included 83 patients in this study. 37/83 patients (44.6%) developed LN with the following urinary signs: 92% of proteinuria (mean 3366.147 mg ± 2785.93 / 24h) including 2/3 of cases of nephrotic syndrome, 81% of hematuria, 14% of acute renal failure with significant reduction in glomerular filtration rate (average creatinine clearance of 32.42 ml / min) and 12% high blood pressure. Out of a total of 30 renal biopsies interpreted at disease diagnosis, 73.4% diffuse proliferative glomerulonephritis forms were observed: (III (30%), IV (36.7%) and VI (6, 7%)). Lupus nephritis were significantly correlated with hypocomplementemia in its C3 (P = 0.00002) and C4 (P = 0.00005) fraction, lymphopenia (P = 0.02), anti-DNA antibodies (P = 0.026), SLEDAI (P = 0.00001) and mortality (P = 0.03). The most frequently used induction drugs for LN classes III, IV and VI were pulsed intravenous methylprednisolone (500 mg daily for 3 doses) in combination with low dose intravenous cyclophosphamide (23%) in the short term (500 mg/m2/15 days X 6) followed by mycophenolate mofetil (28%) (600mg/ m2 in two daily doses) as maintenance treatment associated with a daily dose of oral glucocorticoids with a gradual decrease until reaching the minimum amount necessary to control the disease. All of our SLE patients with nephritis were treated with HCQ with a significant correlation with the decrease in SLEDAI. During the first two years of disease progression, the frequency of LN increased to 43/83 (51.8%) mainly in these severe forms: (IV (41.7%), V (2.8 %). The progression to chronic renal failure had a prevalence of 6, 9% (3/43) of cases; these were mainly patients with severe lupus nephritis (III, and IV) Conclusion Nephritis is a major risk factor for morbidity and mortality in pSLE; LN in children is most often proliferating and more active. The early diagnosis and management of kidney damage are the only guarantee of a good course and prevention of the progression of chronic renal failure. Keywords lupus nephritis; child; systemic lupus erythematosus; disease activity, mortality.

Revisiting vasculopathy in lupus nephritis: A renal biopsy evaluation study

Introduction:The classification of lupus nephritis (LN) on biopsy is essentially focused on morphologic changes in glomeruli. Renal vascular lesions are not addressed in detail in current classifications and are often overlooked. We aimed to determine the prevalence of vascular lesions in LN on biopsies and to compare these with biopsies not showing the vasculopathies.Methods:A total of 740 renal biopsies of LN were analysedfor presence of vasculopathies from January 2013 to June 2019. Of these, 527 (71.2%) biopsies showed vascular lesions (vascular group), which were further categorized into known five subtypes according to morphology and immunofluorescence (IF) findings. Remaining 213 (28.8%) biopsies constituted non-vascular group. Clinical, demographic and laboratory parameters were compared between these two groups.Results:The mean age was 27.95 ± 9.8 years and 27.0 ± 9.4 years in the vascular and non-vascular groups respectively with higher M:F (1:2 > 1:7) in vascular group. Majority of vasculopathies (257, 48.7%) were found in biopsies with class IV LN. Haematuria (69.8% vs. 20.1%), proteinuria (100% vs. 62%), anemia (48.3% vs. 3.60%) and hypertension (39.8% vs. 8.46%) were common in group I. Uncomplicated vascular immune deposits (426; 80.8%) were the most common vasculopathy and true vasculitis (4;0.8%) was least common. Activity and chronicity indices (7.35 ± 3 and 2.45 ± 1.5, respectively) were significantly higher in the vascular group. Activity index was highest in uncomplicated vascular immune deposits (7.45 ± 2.8) and chronicity index was highest in non-specific sclerotic vascular lesions (2.7 ± 1.6).Conclusion:Vascular involvement is common in LN. Uncomplicated vascular immune deposits were common vasculopathies whereas true vasculitis was least common. The morphology and IF both need to be carefully screened for the diagnosis of vasculopathies.

A study on the relationship between morphological lesions of lupus nephritis with demographic and biochemical findings

Introduction: Lupus nephritis is one of the important aspects of systemic lupus erythematosus (SLE). Objectives: This study aimed to investigate possible relationship between pathological lesions of lupus nephritis classes and demographic and biochemical findings among patients. Patients and Methods: This is a cross-sectional study that was conducted on a group of renal biopsy proven lupus nephritis patients using lupus nephritis classification of ISN/RPS 2003. We collected demographic data of all patients including age, gender serum creatinine and 24h proteinuria. Results: Data of 101 patients, of whom 78 (77.23%) were females and mean age of 33.54±13.15 years. The mean serum creatinine and proteinuria were 1.54±0.88 mg/dL 2502.5±1495.05 mg/d. Based on our data, IV-G (class IV, diffuse lupus nephritis-global) lupus nephritis class was the most common (39.6%) followed by class III (23.8%). The mean crescent and sclerotic glomeruli were 1.66±3.32 and 2.27±5.32, respectively. In this study, 24 hours proteinuria, serum creatinine, activity percent, chronicity percent, crescent and glomerular sclerosis between genders showed no significant differences (P&gt;0.05). The correlation between plasma creatinine and activity was directly positive and significant (r=0.381, P=0.001). In addition, a significant correlation between C1q deposits and glomerular sclerosis (P=0.031) was detected. Accordingly, a significant correlation between IgG deposits and lupus nephritis classification (P=0.025) was seen. Conclusion: Lupus nephritis of IV-G and III classes of lupus nephritis were most common among patients and higher IgG deposits were observed in patients with IV-G classification. We found a significant correlation between glomerular sclerosis and C1q deposits that could be an indicator of lupus nephritis activity and severity. However, we recommend further studies in this regard.

Predicting lupus membranous nephritis using reduced picolinic acid to tryptophan ratio as a urinary biomarker

SummaryThe current gold standard for classifying lupus nephritis (LN) progression is a renal biopsy, which is an invasive procedure. Undergoing a series of biopsies for monitoring disease progression and treatments is unlikely suitable for patients with LN. Thus, there is an urgent need for non-invasive alternative biomarkers that can facilitate LN class diagnosis. Such biomarkers will be very useful in guiding intervention strategies to mitigate or treat patients with LN. Urine samples were collected from two independent cohorts. Patients with LN were classified into proliferative (class III/IV) and membranous (class V) by kidney histopathology. Metabolomics was performed to identify potential metabolites, which could be specific for the classification of membranous LN. The ratio of picolinic acid (Pic) to tryptophan (Trp) ([Pic/Trp] ratio) was found to be a promising candidate for LN diagnostic and membranous classification. It has high potential as an alternative biomarker for the non-invasive diagnosis of LN.

Time to Recovery From Proteinuria and Its Related Factors in Patients With Lupus Nephritis

Lupus nephritis (LN) is a severe form of systemic lupus erythematosus (SLE) with renal involvement. It affects the kidneys in about 50% of SLE patients. The aim of this study was to assess the evaluation of proteinuria recovery time and its related factors associated with lupus nephritis patients in Urmia-Northwest of Iran. A retrospective cohort study was carried out, in which medical records of 80 patients with systemic lupus nephritis referred to Imam Khomeini university hospital were reviewed. According to these records, the biopsy-proven renal disease has been progressed from September 2009 to September 2013. Proteinuria, less than 0.5 g/24h, was defined as proteinuria recovery. The time elapsed from the diagnosis of proteinuria to its recovery is considered as the duration of proteinuria recovery (month). The findings were analyzed by STATA11 statistical software. The mean age at diagnosis of lupus nephritis was 26.50±8.10 years (14-51 years). The mean creatinine level at the start of treatment was 1.20±0.61 mg/dl (0.5-2.80). Proteinuria recovery time was four months for 25% of patients, six months for 50% of patients (median time), and 12 months for 75% of them. The higher class of LN had a trend toward 31 % lower risk of proteinuria recovery (HR: 0.73, 95% CI 0.56-0.96; P=0.02), the expected risk is 1.94 times greater in women as compared with men (HR: 1.94, 95% CI 1.1-3.48; P=0.02). The patients in this study population respond to treatment in less time, and in comparison with other studies, their proteinuria recovers earlier. Class of lupus nephritis (negative) and gender (positive) were predictive factors of proteinuria recovery among LN patients.

Clinical Differences in Lupus Nephritis in Thai Patients with Systemic Lupus Erythematosus with Positive vs. Negative Anti-dsDNA Antibody

Objective: Anti-double strand deoxyribonucleic antibody (anti-dsDNA) is thought to trigger tissue inflammation-particularly in the kidney-in systemic lupus erythematosus (SLE). The association between anti-dsDNA and lupus nephritis (LN) has not been reported among Thais. The authors aimed to define the association between the clinical characteristics of positive vs. negative antidsDNA antibody in patients having SLE with LN. Materials and Methods: A historical cohort was conducted of SLE patients followed-up at Srinagarind Hospital, Khon Kaen University, Thailand, between January 2009 to December 2013. The authors excluded patients not tested for anti-dsDNA. Results: Of 132 SLE patients, the female was 123 cases. The respective mean age at onset and mean age during the study was 28.0&plusmn;11 and 35.2&plusmn;11.2 years. The mean duration of disease was 5.7&plusmn;4.7 years. Ninety-six cases were tested for anti-dsDNA, of whom 73 (76%) were positive. There was a significant association between the presence of anti-dsDNA antibody and subnephrotic range proteinuria (p=0.048) and negative association with LN class IV A/C at onset (p=0.04). Conclusion: Anti-dsDNA was positive in around three-quarters of Thai SLE patients and the presence of the antibody was associated with renal involvement, particularly subnephrotic range proteinuria. Keywords: Systemic lupus erythematosus; Autoimmune diseases; Anti-dsDNA antibody; Lupus nephritis; Proteinuria

Change of Renal Gallium Uptake Correlated with Change of Inflammation Activity in Renal Pathology in Lupus Nephritis Patients.

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.

English

BACKGROUND Lupus nephritis (LN) is very common and significantly affects the prognosis of patients with systemic lupus erythematosus (SLE). Although the diagnosis of LN is obvious sometimes from the simple lab tests, it is important to perform a renal biopsy. We wanted to study the correlation between the clinical, lab parameters and the histopathological grade of LN in a tertiary care centre in South India. METHODS A cross-sectional study was conducted among all patients with biopsy proven LN who underwent a renal biopsy from 19 / 09 / 2017 to 30 / 06 / 2019. Data of 51 patients were obtained. For all the study subjects, a history was obtained, clinical examination was done, and their lab parameters and the renal biopsy report were noted in the proforma. The histology was correlated with the laboratory and clinical data. RESULTS The majority of the patients were females. Maximum patients had class IV LN and class III had more males than any other class of LN. When clinical and laboratory parameters were correlated with histopathological findings, pedal oedema and facial puffiness were found to be correlated with the classes of lupus nephritis with statistical significance. Among investigations, haemoglobin, C3, activity score and 24 -hour urine protein had a statistically significant correlation with the various classes of lupus nephritis. CONCLUSIONS This study suggests some meaningful correlation between pedal oedema, facial puffiness, 24 hours urine protein, haemoglobin levels, C3 levels and activity score with lupus nephritis classes of ISN / RPS 2003 classification. KEY WORDS Lupus, Clinicopathological Correlation

Treatment Outcomes of Proliferative vs. Non-proliferative Adult Lupus Nephritis: A 10-Year Follow-Up.

IntroductionSystemic lupus erythematosus (SLE) is a systemic disease with clinically heterogeneous outcomes. Lupus nephritis (LN) is a common complication of SLE. LN impacts clinical SLE outcomes both directly, in the form of target organ damage, and indirectly, through the adverse effects of immunosuppressive therapy.Patients & methodsThe study included 402 SLE cases with biopsy-proven lupus nephritis who were under follow-up for the past 13 years at Mansoura Urology and Nephrology Center, Egypt. We studied the differences in outcome among various LN classes and between 275 proliferative cases and 102 non-proliferative cases.ResultsClass IV was the main LN class in our series with renal survival of 60% at 10 years. The major induction regimen after the first biopsy was cyclophosphamide. Mycophenolate mofetil was the main induction and adjunctive regimen after the second biopsy. The mean follow-up period was 6.7 + 5.2 years. Higher serum creatinine, proteinuria, activity, and chronicity indices were noted in proliferative LN. Patients suffering from proliferative lesions received higher immunosuppression and demonstrated higher morbidity than those with non-proliferative lesions. Remission was higher among the non-proliferative compared to the proliferative group.ConclusionsSerum creatinine, proteinuria, and LN class were the most relevant prognostic factors for renal survival among Egyptian LN patients.

Coincidental light chain induced proximal tubulopathy with lupus nephritis: a\xa0case report and review of the\xa0literature

BackgroundWe report a case of light chain proximal tubulopathy associated with lupus nephritis in a patient known to have systemic lupus erythematosus. The kidney can be injured in several ways in any of these disorders. Light chain proximal tubulopathy is a rare form of renal tubular injury that may occur in and complicate plasma cell dyscrasia, characterized by cytoplasmic inclusions of the monoclonal light chain within proximal tubular cells. Lupus nephritis is a common form of renal injury as it occurs in about 25–50% of adult patients with systemic lupus erythematosus.Case presentationWe present a 57-year-old African patient known to have systemic lupus erythematosus and hypertension presented with a new complaint of microscopic hematuria. A renal biopsy was performed and revealed lupus nephritis class II concurrently associated with light chain induced proximal tubulopathy. A subsequent bone marrow biopsy was performed, which revealed multiple myeloma.ConclusionsWe report a case of coincidental lupus nephritis and proximal tubulopathy featuring a combined constellation of rare histopathological features that might add to the relationship between systemic lupus and paraproteinemia.

Remission after Six Months of Induction Immunosuppressive Treatment with Mycofenolate Mofetil and Prednisolone in Patients with Lupus Nephritis: A Descriptive Cross-sectional Study.

Treatment of lupus nephritis consists of six months of induction immunosuppression followed by years of maintenance immunosuppression. The aim of present study was to find the prevalence of remission after six months of induction immunosuppressive treatment with induction therapy in patients with lupus nephritis. A descriptive cross-sectional study was conducted in the nephrology unit of department of internal medicine of a tertiary care hospital from September 2018 to September 2020. The study was approved by institutional review committee of same institution (reference number 184/2018). Convenience sampling method was used and Statistical Package for Social Sciences version 26 was used for statistical analysis. Point estimate at 90% Confidence Interval was calculated along with frequency and proportion for binary data. Out of 24 patients, overall remission was seen in 21 patients (87.4%) (90% Confidence Interval= 76.26-98.54). Complete remission and partial remission were seen in 16 (66.6%) and 5 (20.8%) patients respectively resulting in an at the end of six months of induction immunosuppressive treatment. The most common class of lupus nephritis was class IV, 7 patients, followed by class IV+V, and class V, 6 patients in each respectively. The mean 24-hour urinary total protein, serum albumin and serum creatinine were 2492±1051 mg, 2.1±0.4 g/dl, and 0.9±0.1 mg/dl respectively. Adverse events were observed in 6 (25%) patients. Our study shows that good proportions of patients with lupus nephritis achieve clinical remission at the end of six months of induction immunosuppressive treatment with induction therapy, however, at the cost of some tolerable side effects.

Treatment outcomes in refractory lupus nephritis: Data from an observational study.

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. 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. 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. 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.

Association between tubulointerstitial CD8+T cells and renal prognosis in lupus nephritis

ObjectiveInflammatory cell infiltration is a pathological change commonly seen in renal biopsies from patients with lupus nephritis(LN), but its clinicalcorrelationwith clinical parameters and prognosis is unclear. MethodsIncluded in this retrospective study were 197 patients with ISN/ RPS Class III-V LN, in whom renal biopsy was performed to analyze the histological pattern. Tubulointerstitial infiltrates were quantitated by standard histochemical staining. Clinical and histologic variables were evaluated using a Cox proportional hazards model. End-stagerenaldisease(ESRD) progression was defined as a two-fold increase in serum creatinine (SCr) after biopsy, GFR decreased over 40%, initiation of dialysis, transplantation, or death. ResultsOf the 197 patients, 166 patients (84.3%) had proliferative LN. The number of tubulointerstitial infiltrates was the lowest in LN patients with ISN/RPS class V, and the number of CD68+ macrophages was the highest in all ISN/RPS classes of LN. In addition, the number of CD8+T cell infiltrates was positively correlated the SLEDAI sore, SCr level, proteinuria, the ratio of glomerulosclerosis and the degree of tubulointerstitial inflammation, interstitial fibrosis and tubular atrophy, activity and chronicity indices, and negatively correlated with C3 level at presentation. Multivariate survival analysis showed that tubulointerstitial CD8 + T cells > 130/mm2 was associated with ESRD progression (HR 1.007; 95% CI 1.003 to 1.011; p < 0.001). ConclusionTubulointerstitial CD8+T cells correlate with clinicohistologic impairment in LN. Tubulointerstitial CD8+T cells > 130/mm2 is independently associated with an unfavorable long-term kidney outcome.

An Update on the Management of Childhood-Onset Systemic Lupus Erythematosus.

Childhood-onset systemic lupus erythematosus (cSLE) is a prototype of a multisystemic, inflammatory, heterogeneous autoimmune condition. This disease is characterized by simultaneous or sequential organ and system involvement, with unpredictable flare and high levels of morbidity and mortality. Racial/ethnic background, socioeconomic status, cost of medications, difficulty accessing health care, and poor adherence seem to impact lupus outcomes and treatment response. In this article, the management of cSLE patients is updated. Regarding pathogenesis, a number of potential targets for drugs have been studied. However, most treatments in pediatric patients are off-label drugs with recommendations based on inadequately powered studies, therapeutic consensus guidelines, or case series. Management practices for cSLE patients include evaluations of disease activity and cumulative damage scores, routine non-live vaccinations, physical activity, and addressing mental health issues. Antimalarials and glucocorticoids are still the most common drugs used to treat cSLE, and hydroxychloroquine is recommended for nearly all cSLE patients. Disease-modifying antirheumatic drugs (DMARDs) should be standardized for each patient, based on disease flare and cSLE severity. Mycophenolate mofetil or intravenous cyclophosphamide is suggested as induction therapy for lupus nephritis classes III and IV. Calcineurin inhibitors (cyclosporine, tacrolimus, voclosporin) appear to be another good option for cSLE patients with lupus nephritis. Regarding B-cell-targeting biologic agents, rituximab may be used for refractory lupus nephritis patients in combination with another DMARD, and belimumab was recently approved by the US Food and Drug Administration for cSLE treatment in children aged > 5 years. New therapies targeting CD20, such as atacicept and telitacicept, seem to be promising drugs for SLE patients. Anti-interferon therapies (sifalimumab and anifrolumab) have shown beneficial results in phase II randomized control trials in adult SLE patients, as have some Janus kinase inhibitors, and these could be alternative treatments for pediatric patients with severe interferon-mediated inflammatory disease in the future. In addition, strict control of proteinuria and blood pressure is required in cSLE, especially with angiotensin-converting enzyme inhibitor and angiotensin receptor blocker use.