Remission Of Lupus Nephritis Research Articles

Clinicopathological correlation of patients with lupus nephritis: Data from a tertiary center in Saudi Arabia.

Systemic lupus erythematosus mainly affects young women, and approximately half of systemic lupus erythematosus patients develop lupus nephritis (LN). However, data on the types and remission rates of LN in Saudi Arabia are limited. Therefore, we aimed to highlight the LN remission rates in our population. A retrospective record review was conducted between January 2007 and December 2020 in a tertiary center in the western region of Saudi Arabia to determine the remission rates among patients with biopsy-proven LN who met the EULAR\ACR 2019 classification criteria. We identified 59 patients with biopsy-proven LN, mostly in young women. The common histopathological pattern was Class IV LN in 26 patients (44%). Three induction protocols were identified, along with systemic steroids: the high-dose cyclophosphamide protocol in 21 patients (35.6%), low-dose protocol in 4 patients (6.8%), and mycophenolate mofetil (MMF) in 41 patients (69.5%). Partial response, defined as the reduction of the 24-hour proteinuria by 25% at 3 months and 50% at 6 months, was achieved in 18 patients (33.3%) at 3 months and decreased to 13 patients (24.1%) at 6 months. Complete clinical response, defined as 24-hour urinary protein between 500 and 700 mg at 12 months, was achieved in 44 patients (81.5%). Complete remission was higher among patients with Class IV LN (64.4%). The achievement of partial clinical response at 3 months was significantly lower among patients with hypertension (P = .041). This study presented the LN remission rates in a single center in Saudi Arabia. Similar to previous studies, Class IV LN were the most common histopathological finding in this study. Complete remission at 12 months was achieved in 44 (81%) patients. Delayed remission is associated with hypertension at the time of LN diagnosis.

Anti-C1q antibodies: a biomarker for diagnosis and management of lupus nephritis. A narrative review.

Nephritis is a frequent and severe complication of Systemic Lupus Erythematous (SLE). The clinical course of lupus nephritis (LN) is usually characterized by alternating phases of remission and exacerbation. Flares of LN can lead to deterioration of kidney function, necessitating timely diagnosis and therapy. The presence of autoantibodies against C1q (anti-C1qAb) in the sera of SLE patients has been reported in various studies. Some research suggests that the presence and changes in the titer of anti-C1qAb may be associated with the development of LN, as well as with LN activity and renal flares. However, theexact role of anti-C1qAb in LN remains a subject of debate. Despite variability in the results of published studies, anti-C1qAb hold promise as noninvasive markers for assessing LN activity in SLE patients. Measuring anti-C1qAb levels could aid in diagnosing and managing LN during periods of both inactive disease and renal flares. Nevertheless, larger controlled trials with standardized laboratory assays are necessary to further establish the utility of anti-C1qAb in predicting the reactivation and remission of LN and guiding treatment strategies.

Determination of nutrition index and correlation with activity of lupus nephritis

Background/Aim. Lupus nephritis (LN), as an immuno-inflammatory kidney lesion, and the most serious manifestation of systemic lupus erythematosus (SLE), is accompanied by a disorder of the nutritional status of patients. Our goal was to determine the importance of determining and the association of parameters of nutritional status - nutritional risk index (NRI), prognostic nutritional index (PNI) and control nutritional status (CONUT) with standard parameters of LN activity. Methods. The clinical study included a group of 92 subjects. 67 patients had LN (34 patients had LN active disease , the LNa group, and 33 patients were in LN remission, the LNr group) and 25 healthy subjects (control group). In addition to standard laboratory parameters, LN activity parameters, derived parameters were also determined: PNI=10 x albumin value (g/dL) + 0.005 x number of peripheral lymphocytes (/mm3); NRI = 1.519 ? serum albumin, g/dL + 41.7 ? weight (kg)/ideal body weight ( kg); CONUT score = serum albumin + total lymphocyte score + total cholesterol. Results. A statistically significant difference between all three groups was observed for the PNI (p=0.001) and for the CONUT score (p=0.000), while the NRI did not have a significant difference. Statistical significance was found for the correlation of PNI in the LNa group, with the levels of albumin, complement C3 and C4, and a significant negative correlation with the value of anti-ds-DNA Ab. NRI correlated with statistical significance only with proteinuria in the LNa group. CONUT showed significant correlations with the most of the parameters for disease activity: negative correlation with albumin and complement C3 (p = 0.000), and positive correlation with anti -double strand (ds) - DNA Antibody (p=0.002),with Systemic Lupus Erythematosus Disease Activity Index/renal (SLEDAI/r) and with proteinuria/24 hrs (p=0.000). Conclusion. In our group of patients, a statistically significant difference was observed between the groups for the nutrition score CONUT. and the PNI. Their correlation with standard parameters of active disease was significant for most parameters in the group of patients with LNa.

The use of belimumab in three cases of refractory lupus nephritis.

In recent trials for the treatment of systemic lupus erythematosus (SLE), belimumab (BLM), in addition to standard immunosuppression, has been shown to improve renal and nonrenal outcomes. We report our experience using BLM in three cases of refractory lupus nephritis (LN), where renal remission was not achieved using cyclophosphamide, mycophenolatemofetil and other immunosuppressive medications. In two of the three cases, BLM therapy led to a partial remission of LN, improvement in serological markers of SLE and disease activity, which permitted a reduction in prednisolone dosing. Treatment with efficacious therapies early in the course of LN is a desirable therapeutic strategy, to achieve early remission of proteinuria and curtail the development of irreversible chronic renal damage. Further studies are needed to provide information on the effectiveness of BLM for maintenance of remission, prevention of flares and monitoring for long-term complications of B-cell modulation.

Remission of lupus nephritis: the trajectory of histological response in successfully treated patients

ObjectiveThis study investigated changes in kidney histology over time in patients with lupus nephritis (LN) undergoing immunosuppressive treatment.MethodsPatients with proliferative±membranous LN were studied. After a diagnostic kidney biopsy (Bx1), patients...

Urine biomarker score captures response to induction therapy with lupus nephritis

BackgroundThe Renal Activity Index for Lupus (RAIL) consists of urine protein assessment of neutrophil gelatinase–associated lipocalin, kidney injury molecule-1, monocyte chemotactic protein 1, adiponectin, hemopexin, and ceruloplasmin, which non-invasively identifies lupus nephritis (LN). We aimed to delineate RAIL scores with inactive versus active LN and changes over time with response to LN induction therapy.MethodsThere were 128 pediatric patients with systemic lupus erythematosus (SLE) and age-matched healthy controls recruited in a prospective case control study, with kidney biopsy confirmation of LN. Laboratory and clinical information was recorded and urine collected at diagnosis and end of induction and during maintenance therapy. Response to therapy was assessed by repeat kidney biopsy or laboratory parameters. Urine was assayed for RAIL biomarkers and the RAIL score calculated.ResultsPediatric RAIL (pRAIL) scores from 128 children and young adults with SLE (with/without LN: 70/38) including 25 during LN induction therapy, differentiated clinically active LN from inactive LN or without LN, and controls (all p < 0.0017). pRAIL scores significantly decreased with complete LN remission by 1.07 ± 1.7 (p = 0.03). ConclusionsThe RAIL biomarkers differentiate LN patients based on activity of kidney disease, with decreases of ≥ 1 in pRAIL scores indicating complete response to induction therapy. Significantly lower RAIL scores in healthy controls and in SLE patients without known LN raise the possibility of subclinical kidney disease.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

Voclosporin Induces Systemic Lipidomic Alterations: Implications in the Remission of Lupus Nephritis

Voclosporin Induces Systemic Lipidomic Alterations: Implications in the Remission of Lupus Nephritis

Serum and Urine Interferon Gamma-Induced Protein 10 (IP-10) Levels in Lupus Nephritis.

Background: Lupus nephritis (LN) is a prevalent and severe complication of systemic lupus erythematosus (SLE). Non-invasive diagnostics are limited, and current therapies have inadequate response rates. Expression of the chemokine Interferon-γ-induced protein 10 (IP-10) is regulated by Interferon-γ signaling and NF-κB, and its molecular activity and enhanced urine concentrations are implicated in LN, but its utility as a diagnostic marker and association with demographic, clinical, or pathologic features is not defined. Methods: 38 LN patients and 11 patients with non-LN glomerular diseases (GD) with active disease were included. Eighteen of the LN patients had achieved remission at one follow-up during the study time. Serum and urine were obtained from these samples, and the IP-10 levels were measured. Results: Serum and urine IP-10 levels are significantly enhanced in LN patients with active disease as compared with normal individuals (serum average 179.7 pg/mL vs. 7.2 pg/mL, p < 0.0001; urine average 28.7 pg/mg vs. 1.6 pg/mg, p = 0.0019) and patients with other forms of glomerular disease (serum average 179.7 pg/mL vs. 84.9 pg/mL, p = 0.0176; urine average 28.7 pg/mg vs. 0.18 pg/mg, p = 0.0011). Urine IP-10 levels are significantly higher in patients with proliferative LN (PLN) than those with membranous LN (MLN) (average 32.8 pg/mg vs. 7.6 pg/mg, p = 0.0155). Urine IP-10 levels are also higher in MLN versus primary membranous nephropathy (MN) (average 7.6 pg/mg vs. 0.2 pg/mg, p = 0.0193). Importantly, serum IP-10 levels remain elevated during active LN and LN remission, but urine IP-10 levels are decreased from active LN to remission in 72% of our patients. Lastly, serum, but not urine IP-10 levels are significantly higher in African American than White American LN patients in active LN (average 227.8 pg/mL vs. 103.4 pg/mL, p = 0.0309) and during LN remission (average 254.6 pg/mL vs. 89.2 pg/mL, p = 0.0399). Conclusions: Our findings suggest that serum and urine IP-10 measurements provide promising tests for monitoring LN activity, differentiation between classifications of LN, and differentiation between LN and other forms of glomerular disease. We also conclude that further assessment of elevated IP-10 levels in the serum and urine of high-risk populations (i.e., African American) could be beneficial in determining why many of these patients have worse outcomes and are non-responsive to standard therapeutics.

Comparative Effectiveness of Rituximab and Common Induction Therapies for Lupus Nephritis: A Systematic Review and Network Meta-Analysis.

ObjectiveThis study aimed to compare the efficacy and safety (infection events) between rituximab (RTX), tacrolimus (TAC), mycophenolate mofetil (MMF), and cyclophosphamide (CYC) as induction therapies in lupus nephritis (LN).MethodsElectronic databases, including PubMed, EMBASE, and the Cochrane Library, were searched from inception up to December 9, 2021. Bayesian network meta-analysis was used to combine the direct and indirect evidence of different drugs for LN patients. The pooled relative effects were shown using odds ratios (ORs) and 95% credible intervals (CrIs).ResultsNineteen studies (1,566 patients) met the inclusion criteria and were selected in the present study. The network meta-analysis reported that no statistically significant differences were found in partial remission (PR) and infection among the four drugs. RTX showed a significantly higher complete remission (CR) than MMF (OR = 2.60, 95% CrI = 1.00–7.10) and seemed to be more effective than CYC (OR = 4.20, 95% CrI = 1.70–14.00). MMF had a better CR than CYC (OR = 1.60, 95% CrI = 1.00–3.20). TAC presented a better overall response than CYC (OR = 3.70, 95% CrI = 1.20–12.00). Regarding CR and overall response, the maximum surface under the cumulative ranking curve (SUCRA) values were 96.94% for RTX and 80.15% for TAC. The maximum SUCRA value of infection reaction was 74.98% for RTX and the minimum value was 30.17% for TAC, respectively.ConclusionsRTX and TAC were the most effective drugs for induction remission in LN. Among the four drugs, TAC had the lowest probability of infection, and RTX showed the highest probability of experiencing an infection. This meta-analysis could not conclude about other adverse events.

POS-981 PREMATURE OVARIAN FAILURE SECONDARY TO LOW DOSE INTRAVENOUS CYCLOPHOSPHAMIDE IN A YOUNG WOMAN WITH RELAPSED LUPUS NEPHRITIS

Cyclophosphamide (CYC) is a nonspecific cell cycle cytotoxic antiproliferative agent that is used in inducing remission in lupus nephritis (LN) and it also possesses a wide spectrum of toxicities, particularly premature ovarian failure (POF) in woman. Ovarian damage often manifests with amenorrhoea, low estrogen level and increased follicle stimulating hormone (FSH) and luteinizing hormone (LH), which resemble the hormonal changes seen at menopausal woman.

Lupus nephritis with corticosteroid responsiveness: molecular changes of CD46-mediated type 1 regulatory T cells.

The engagement of the complement regulatory proteins CD46 and CD3 in human CD4+ T cells induces the type 1 regulatory T cells (Tr1) and interleukin-10 (IL-10) secretion. This study aimed to elucidate the molecular changes of Tr1 cells through CD46 cytoplasmic Cyt1 tail in lupus nephritis (LN) respond to intravenous methylprednisolone (ivMP) therapy. We enrolled 40 pediatric patients with LN and 30 healthy controls. Clinical characteristics and peripheral blood mononuclear cells were collected before and 3 days after the administration of ivMP. Kidney specimens were taken from five LN and five minimal-change nephrotic syndrome patients. We found that defective CD46-mediated T-helper type 1 contraction (IL-10 switching) is present in active LN patients. The ivMP therapy enhanced LN remission, restored the production of IL-10, increased the CD46-Cyt1/Cyt2 ratio, AKT, and cAMP-responsive element-binding protein phosphorylation, and induced migration with the expression of chemokine receptor molecules CCR4, CCR6, and CCR7 of CD3/CD46-activated Tr1 cells. Pharmacologic interventions that alter the patterns of CD46-Cyt1/Cyt2 expression and the secretion of IL-10 by CD3/CD46-activated Tr1 cells can be used in patients with active LN. In patients with LN, ivMP was associated with increased IL-10 production and increased CD46-Cyt1/Cyt2 ratio and AKT phosphorylation by Tr1 cells, with enhanced potential to migration in response to CCL17. These results suggest that expression levels of CD46 isoforms Cyt1 and Cyt2 in CD4 + CD46 + Tr1 cells differ in patients with active LN but can be corrected by corticosteroid treatment. Enhancing the expression of functional CD4 + CD46 + Tr1 cells may be a useful therapeutic approach for LN.

Novel Effects of Combination Therapy Through Inhibition of Caspase-1/Gasdermin D Induced-Pyroptosis in Lupus Nephritis.

ObjectivesCombination therapy with mycophenolate mofetil, tacrolimus and steroids are effective in achieving complete remission in lupus nephritis (LN). Combination therapy uniquely downregulated caspase-1 compared with monotherapies, which can cleave gasdermin D (GSDMD) and was recently identified as the pyroptosis executioner. We therefore investigated whether combination therapy enabled the suppression of caspase-1/GSDMD-mediated pyroptosis in LN.MethodsExpression and activation of GSDMD were detected in kidney specimens of the human and mouse with LN using immunohistochemical staining and immunoblotting. Primary podocytes isolated from MRL/lpr mice were incubated with LPS+ATP, and pretreated with monotherapy or combination therapy. Inhibition of caspase-1/GSDMD-induced pyroptosis by combination therapy were assessed in MRL/lpr mice and human specimens. Pyroptosis was examined using a FAM caspase-1 kit and flow cytometry. The correlation between pyroptosis in peripheral blood and the systemic lupus erythematosus disease activity index (SLEDAI) was analyzed.ResultsKidney tissue specimens from LN patients and mice exhibited greatly increased expression levels and cleavage of GSDMD. In cultured podocytes, combination treatment significantly suppressed the activation of NLRP3 and caspase-1 and reduced GSDMD N-terminal levels. Combination therapy repressed disease progression through inhibition of caspase-1/GSDMD-mediated pyroptosis in both humans and MRL/lpr mice. Caspase-1/PI positive cell numbers in peripheral blood were positively correlated with SLE-DAI. LN patients with complete remission and partial remission had remarkably reduced caspase-1/PI positive cell numbers compared to baseline. Ac-FLTD-CMK, a GSDMD-derived inhibitor, prevented the development of LN.ConclusionCombination therapy suppressed caspase-1/GSDMD-mediated pyroptosis in vitro and in vivo and reduced disease progression.

Serum Renalase Level as A Marker of Activity and Severity in Lupus Nephritis Cases

- Introduction: &nbsp;&nbsp;Lupus nephritis (LN) is a substantial risk factor for death and morbidity in patients with Systemic Lupus Erythematosus (SLE) (SLE). Despite excellent immunosuppressive therapy, it nevertheless leads to a disproportionate percentage of persons developing chronic kidney disease (CKD) or end-stage renal disease (ESRD). Renalase is a distinctive cytokine-like protein generated by the kidneys that promote cell survival. It has been recently linked to the etiology of LN and may be an ideal candidate as a sensitive biomarker&nbsp;for flare-ups and LN remission. -Aim of the work: &nbsp;The purpose of this study was to evaluate the utility of human serum renalase as a biomarker for assessing disease activity and severity in SLE, as well as to evaluate if it can be used as a sensitive biomarker in this capacity. -Methods: &nbsp;This study consists of around 23 healthy controls and 46 individuals with LN. These participants were separated into two equal groups according to disease activity as determined by the SLEDAI (SLE Disease Activity Index): 23 cases with LN who had disease activity and 23 cases who did not. The concentration of human serum Renalase (RNLS) was evaluated using a very sensitive commercial enzyme immunoassay that captures renalase from serum using (RNLS) antibody. - Results: Renalase concentrations were significantly greater in LN cases than in healthy controls (P-value &lt;0.001). Additionally, cases with active LN exhibited significantly greater serum renalase concentrations than those with inactive LN (P-value &lt;0.005). Serum renalase concentrations were positively connected with 24-h urine protein excretion,&nbsp;SLEDAI,&nbsp;ESR, CRP, and ds-DNA but were negatively related to serum C3 and the class (particularly in the proliferative type) (Class III, IV, more than class V). -Conclusion: &nbsp;Serum renalase levels were associated with disease symptoms&nbsp;in LN and may serve as a biomarker for disease activity in LN.

Successful therapeutic response with sequential therapy of rituximab and belimumab in a hispanic patient with refractory lupus nephritis

Lupus nephritis (LN) is the most common severe organ manifestation of systemic lupus erythematosus (SLE). Life expectancy and renal survival is reduced in these patients. A partial remission in LN is associated with a significantly better patient and renal survival rate compared with no remission. We report the case of a 27-year-old Hispanic patient with diffuse proliferative lupus nephritis (grade IV with high activity index) managed with induction therapy with mycophenolate mophethyl (MMF, 1000 mg daily escalating to 3000 mg daily and prednisone (PDN) 1 mg/kg/day. Progression of proteinuria with preserved renal function and extra-renal activity were observed (alopecia). Re-induction with IV cyclophosphamide (CYC, 1 gr.) and pulse IV methylprednisolone (500 mg for three days) was administered, followed by a lower starting dose of PDN (0.5 mg/kg/day). Treatment failure was observed. A second renal biopsy evidenced renal damage (chronicity index 4/12 and activity index 4/24). The patient also developed non-renal clinical manifestations (malar rash, oral ulcers and arthritis). Treatment with IV rituximab (RTX) 1000 mg X2 associated with MMF 1000 mg per day and IV methylprednisolone 500 mg X3 was initiated, followed by PDN 0.5 mg/kg/day with a dose-tapering scheme similar to CYC re-induction. Treatment continued with IV Belimumab (BLM) 600 mg every month associated with MMF 1000 mg per day. Sequential therapy with RTX + BLM showed a partial renal and complete extra-renal response in a patient with severe lupus despite two 2 immunosuppressive treatment schemes.

Hydroxychloroquine use and blood pressure below 130/80 are associated with remission in lupus nephritis: A cohort study

IntroductionThe treatment of lupus nephritis, in addition to immunosuppression, includes the use of adjuvant therapies (antimalarials, statins, blockade of the renin–angiotensin system, and the achievement of blood pressure levels below 130/80). The evidence for the use of these strategies comes from non-autoimmune primary glomerulopathies and there is no information on their impact on the remission of this condition. ObjectiveTo determine, in patients with lupus nephritis, the use of adjuvant therapies and their association with remission at 12 months. Materials and methodsA retrospective cohort study was conducted, between 2005 and 2012. Patients who achieved complete remission of nephritis were compared with those who did not. Complete remission was defined by the American College of Rheumatology AdHoc Subcommittee. OutcomesPercentage of use of adjuvant therapies. Bivariate and multivariate analysis were performed to define association with remission. Results167 subjects were included (all eligible subjects); 85.6% used antimalarials, 65.5% angiotensin converting enzyme inhibitors, 33.5% angiotensin receptor blockers, 30.7% dual blockade, 29.3% statins, and 85% achieved the goal blood pressure. In the multivariate analysis, the use of hydroxychloroquine (OR=.149; 95% CI: .034–.647; p=.003) and the achievement of goal blood pressure (OR=.248; 95% CI: .1–.615; p=.003) were associated with remission. ConclusionsIn a cohort of patients with lupus nephritis, the use of hydroxychloroquine and achieving blood pressure values lower than 130/80 were associated with remission at 12 months.

CD62L on blood basophils: a first pre-treatment predictor of remission in severe lupus nephritis.

Basophils were recently shown to contribute to lupus nephritis (LN). This study assessed blood basophil activation markers (BAMs) for the diagnosis of LN severity and as pre-treatment prognostic markers of the response to treatment in patients with severe LN. The diagnostic study included all the patients of a monocentric prospective observational cohort built with consecutive patients diagnosed with LN on the basis of a renal biopsy. The prognostic study selected patients of this cohort according to the following inclusion criteria: ≥18 years old, Class III or IV A ± C ± Class V or pure Class V LN at the time of inclusion and treated with an induction treatment for LN. Clinical data and BAMs were obtained at the time of the kidney biopsy. LN remission status was recorded 12 months after induction therapy initiation. Associations between baseline data and histological severity of LN or LN remission were assessed using logistic regression. No significant association was found between BAMs and the histological severity of LN in 101 patients. Among the 83 patients included in the prognostic study, 64 reached renal remission. CD62L expression on blood basophils at baseline was independently negatively associated with remission at 12 months [odds ratio = 0.26, 95% confidence interval 0.08-0.82, P = 0.02 for quantitative CD62L expression >105 (geometric fluorescent intensity) gMFI]. CD62L <105 gMFI was associated with a probability of 0.87 of LN remission in the next 12 months after the start of induction therapy. Pre-treatment CD62L expression on blood basophils could be a first predictive biomarker of renal response to induction therapy at 12 months in patients with severe LN.

Immune Cell Landscape Identification Associates Intrarenal Mononuclear Phagocytes With Onset and Remission of Lupus Nephritis in NZB/W Mice.

ObjectiveA challenging issue in the clinical management of lupus nephritis (LN) is the resistance to immunosuppressive therapy. We postulated that perturbed intrarenal immune cell landscape affected LN onset and remission induction, and shedding light on the characteristics of intrarenal immune cell infiltration could cultivate more efficient treatment regimens.Materials and MethodsGenome-wide expression profiles of microarray datasets were downloaded from the Gene Expression Omnibus database. The CIBERSORT algorithm was used to analyze the intrarenal immune cell landscape, followed by Pearson correlation analysis and principal component analysis. The differentially expressed genes were identified and subjected to Gene Ontology (GO) enrichment analyses and protein-protein interaction network establishment, being visualized by Cytoscape and further analyzed by CytoHubba to extract hub genes. Hub genes were also validated in the genomic dataset from kidney biopsy-proven LN patients.ResultsIn addition to memory B cells, monocytes and M1 macrophages were identified as two predominantly increased intrarenal immune cell types in LN-prone NZB/W mice upon nephritis onset. Most interestingly, apart from memory B cells, monocytes and M1 macrophages proportions in kidney tissue were significantly lower in early remission mice compared with late remission mice. Furthermore, GO analysis showed that intrarenal mononuclear phagocytes triggered nephritis onset mainly via the initiation of adaptive immune response and inflammatory reaction, but this functional involvement was mitigated upon remission induction. Hub genes related to LN onset in NZB/W mice were validated in the genomic dataset from kidney biopsy-proven LN patients.ConclusionLN characterizes aberrant mononuclear phagocytes abundance and signature upon disease onset, of which the reversal is associated with early remission induction in LN-prone NZB/W mice. Mononuclear phagocytes might be an adjunctive histology marker for monitoring disease onset and stratifying LN patients in terms of response to remission induction therapy.

What is the value of repeat kidney biopsies in patients with lupus nephritis?

Recent studies with protocol biopsies have shown a mismatch between clinical and histological remission in lupus nephritis (LN). We aimed to evaluate histological changes in repeat kidney biopsies by clinical indication in patients with LN. We analyzed 107 patients with LN in which a kidney biopsy was performed between 2008 and 2018. Of those, we included 26 (24.2%) who had ≥2 kidney biopsies. Classification was done according to the International Society of Nephrology/Renal Pathology Society. Mean time between biopsies was 71.5 ± 10.7 months. 73.1% of patients presented a change of class at repeat biopsy; 38.4% to a higher class and 34.6% to a lower class. A significant increase in glomerulosclerosis (% GS) (3.8% vs 18.7%, p = 0.006), interstitial fibrosis (3.8% vs 26.9%, p = 0.021), tubular atrophy (15.4% vs 57.7%, p = 0.001) and chronicity index (CI) (1 vs 3, p < 0.001) was observed at repeat biopsy. Subjects who developed chronic kidney disease progression had a lower rate of complete remission at 12 months (0% vs 37.5%, p = 0.02), higher % GS at first biopsy (7.9% vs 1.2%, p = 0.02) and higher CI (4 vs 2, p = 0.006), tubular atrophy (90% vs 37.6%, p = 0.008), interstitial fibrosis (50% vs 12.5%, p = 0.036) and vascular lesions (60% vs 18.8%, p = 0.031) at second biopsy. Our major finding was that patients with LN showed a significant increase in % GS, interstitial fibrosis, tubular atrophy and vascular lesions in repeat biopsies performed by clinical indication. This suggest that a second kidney biopsy may provide valuable and useful information regarding kidney disease progression.

Efficacy of Lower Dose Prednisolone in the Induction of Remission of Lupus Nephritis

Efficacy of Lower Dose Prednisolone in the Induction of Remission of Lupus Nephritis

Urinary Angiotensinogen Predicts Renal Disease Activity in Lupus Nephritis.

Aims: A noninvasive indicator of renal histological lesions and disease activity in lupus nephritis (LN) is needed for timely and targeted treatment before overt renal injury. Here, we tested the utility of urinary angiotensinogen (UAGT) to predict renal disease activity in LN. Results: A prospective, three-stage study was performed in patients with LN. In stage I, UAGT was measured in 140 newly diagnosed LN patients. UAGT significantly increased in LN patients, correlating well with kidney angiotensinogen expression and histological activity. Patients with LN class IV exhibited the highest UAGT compared with other histopathological classes of LN. For identifying LN class IV, a particularly aggressive type of LN, UAGT outperformed the conventional clinical measures and improved their performance. In stage II, UAGT was monitored in 61 subjects from stage I for up to 12 months. UAGT decreased after induction therapy and remained low in patients with LN remission during follow-up. For predicting therapy success at month 12, the area under the receiver operating characteristics curve of UAGT reduction at month 4 was 0.83, outperforming that of 24-h proteinuria. In stage III, UAGT was monitored in 12 LN patients before, during, and after the onset of renal flares. An elevation in UAGT predicted recurrence of LN, and a decline in UAGT after a renal flare heralded the remission of disease before conventional clinical measures. Innovation and Conclusion: UAGT in LN is a promising indicator for dynamic surveillance of renal disease activity and prediction of renal flares. Antioxid. Redox Signal. 31, 1289-1301.