Outcomes Of Lupus Nephritis Patients Research Articles

Clinical outcomes in lupus nephritis patients treated with belimumab in real-life setting: a retrospective comparative study in China.

The use of belimumab in treating lupus nephritis (LN) patients in China is still in its early stages. This retrospective comparative study aims to delineate the disease activity, associated therapies, clinical outcomes, and adverse events among LN patients treated with belimumab, reflecting real-world experience in southeastern China. From May 2020 to December 2023, 54 LN patients treated with belimumab and 42 LN patients treated with conventional therapy were enrolled. All patients had a follow-up period of more than 3 months. The general information, presenting clinical and laboratory data, and outcomes were collected and compared. At 3 months of belimumab treatment, compared to baseline, there was a decrease in proteinuria from 74.1% to 64.8% (p<0.001), a reduction in hematuria from 59.3% to 37.0% (p=0.008), and an increase in partial or complete renal response from 53.7% to 75.9% (p<0.001). The median SLEDAI score decreased from 10 to 5 (p<0.001), and the proportion of patients achieving low lupus disease activity state (LLDAS) increased from 11.11% to 16.67% (p<0.001) by the 3-month evaluation. Notably, there were significant reductions in oral corticosteroid dosages, with a median decrease from 30 to 17.5 mg/day (p<0.001) by 3 months, and the proportion of patients requiring >5 mg/day of steroids decreased from 88.89% at baseline to 79.07% at six months (p<0.001). Compared to the conventional therapy group, the belimumab group experienced a significant reduction in median steroid dosage and increased the proportion of patients achieving remission or LLDAS. The incidence of treatment-emergent adverse events (TEAEs) was significantly lower in the belimumab group (29.6% vs 52.4%, p=0.024). These findings support the potential of belimumab to improve renal and serological parameters, reduce disease activity, lessen corticosteroid dependence, and decrease the risk of TEAEs, demonstrating its safety and efficacy as an adjunct therapy in LN management.

Clinicopathological characteristics and outcomes of lupus nephritis patients with scanty immune depositions in kidneybiopsies.

The clinicopathological features, outcomes, and pathogenesis of lupus nephritis with scanty immune deposits in the kidney biopsy remain unclear. Four hundred ninety-eight biopsy-proven lupus nephritis patients were included, and clinical and pathological data were collected. The primary endpoint was mortality, while the secondary endpoint was doubling baseline serum creatinine or end-stage renal disease. Associations between scanty immune deposits lupus nephritis and adverse outcomes were analyzed by Cox regression models. Among 498 lupus nephritis patients, 81 were diagnosed withscanty immune deposits. Patients with scanty immune deposits had significantly higher serum albumin and serum complement C4 than those with immune complex deposits. The proportion of anti-neutrophil cytoplasmic antibodies was similar between the two groups. In addition, patients with scanty immune deposits showed less proliferativefeatures at kidney biopsy and lower activity index score, accompanied by milder mesangial cell and matrix hyperplasia, endothelial cell hyperplasia, nuclear fragmentation, and glomerular leukocyte infiltration. Patients in this group also had a milder degree of foot process fusion. Overall, renal survival and patient survival showed no significant difference between the two groups. 24-h proteinuria and chronicity index were significantrisk factors for renal survival, and 24-h proteinuria and positive anti-neutrophil cytoplasmic antibodies were risk factors for patient survival in scanty immune deposits lupus nephritis patients. Compared with other lupus nephritis patients, scanty immune deposits lupus nephritis patients had significantly lower activity features on kidney biopsy, but have similar outcomes. Positive anti-neutrophil cytoplasmic antibodies may be a risk factor for patient survival in scanty immune deposits lupus nephritis patients.

Long-term impact of pregnancy on renal function among Egyptian women with lupus nephritis: A case control study.

Few studies tackled the long-term effect of pregnancy on lupus nephritis (LNs); thus, the study aimed to explore the long-term impact of pregnancy on renal outcomes in Egyptian patients with LN. Group I patients included females who had their first pregnancy after LN onset with ≥5years elapsing after delivery; group II patients included females who had never got pregnant for ≥7years after LN onset. Data were retrospectively collected at baseline (T0) and the last visit (Tlast). The study included 43 patients in group I and 39 patients in group II. The comparisons between the two groups regarding the characteristics at Tlast showed no significant difference regarding the serum creatinine, estimated glomerular filtration rate (eGFR), renal component of SLICC/ACR Damage Index (SDI) as well as the rate of renal flares, new-onset chronic kidney disease (CKD), progressed CKD and end-stage renal disease. Multivariate regression analysis revealed that systemic hypertension and renal flares were predictors of new-onset/progressed CKD (p = 0.019, OR [95% CI] = 4 [1.3-13]; and 0.022, 13.8 [1.5-128.8], respectively) while pregnancy was not (p = 0.363). Paired comparisons between T0 and Tlast characteristics within each group revealed significant increment of serum creatinine, renal SDI and CKD prevalence; as well as decrement of eGFR in group I (p = 0.004, <0.001, 0.001 and <0.001, respectively) and group II (p = 0.006, <0.001, 0.004 and 0.002, respectively). In conclusion, pregnancy, per se, does not affect the long-term renal outcome in LN patients; however, it is rather dependent on the existence of baseline renal damage and the development of renal flares.

Association between glomerular mTORC1 activation and crescents formation in lupus nephritis patients.

This study aims to explore the association between glomerular mammalian target of rapamycin complex 1 (mTORC1) pathway activation and crescents' degree in lupus nephritis (LN) patients. A total of 159 biopsy-proven LN patients were enrolled in this retrospective study. The clinical and pathological data of them were collected at the time of renal biopsy. mTORC1 pathway activation was measured by immunohistochemistry, expressed by the mean optical density (MOD) of p-RPS6 (ser235/236), and multiplexed immunofluorescence. The association of mTORC1 pathway activation with clinico-pathological features especially renal crescentic lesions, and the composite outcomes in LN patients was further analyzed. mTORC1 pathway activation could be detected in the crescentic lesions and was positively correlated with the percentage of crescents (r=0.479, P<0.001) in LN patients. Subgroup analysis showed mTORC1 pathway was more activated in patients with cellular or fibrocellular crescentic lesions (P<0.001), but not fibrous crescentic lesions (P=0.270). The optimal cutoff value of the MOD of p-RPS6 (ser235/236) was 0.0111299 for predicting the presence of cellular-fibrocellular crescents in >7.39% of the glomeruli by the receiver operating characteristic curve. Cox regression survival analysis showed that mTORC1 pathway activation was an independent risk factor for the worse outcome (defined by composite endpoints of death, end-stage renal disease and a decrease of >30% in eGFR from baseline). Activation of mTORC1 pathway was closely associated with the cellular-fibrocellular crescentic lesions and could be a prognostic marker in LN patients.

Association between serum uric acid level and systemic lupus erythematosus kidney outcome: An observational study in Southern Chinese population and a meta-analysis.

The study aimed to explore the effect of serum uric acid (SUA) level on the progression of kidney function in systemic lupus erythematosus (SLE) patients. A total of 123 biopsy-proven lupus nephritis (LN) patients were included in this retrospective observational study. Cox proportional hazard regression analyses as well as restricted cubic spline analyses were performed to identify predictors of renal outcome in LN patients. We also performed a systematic review and meta-analysis for SUA and overall kidney outcomes in SLE patients. Based on the laboratory tests at renal biopsy, 72 (58.5%) of the 123 patients had hyperuricemia. The median (IQR) follow-up duration was 3.67years (1.79-6.63years), and a total of 110 (89.4%) patients experienced progression of LN. Increased serum uric acid level, whether analyzed as continuous or categorical variable, was associated with higher risk of LN progression in Cox proportional hazard regression model (hazard ratio [HR]: 1.003, 95% confidence interval [CI]: 1.001-1.005; HR: 1.780, 95% CI: 1.201-2.639, respectively). This relationship maintained in women (HR: 1.947, 95% CI: 1.234-3.074) but not men (HR: 2.189, 95% CI: 0.802-5.977). The meta-analysis showed a similar result that both continuous and categorical SUA were positively associated with the risk of kidney function progression in LN (weighted mean difference [WMD]: 1.73, 95% CI: 0.97-2.49; odds ratio [OR]: 1.55, 95% CI: 1.20-2.01, respectively). Our study found overall and especially in women that higher SUA in LN patients were associated with increased risk of renal progression. Meta-analysis yielded consistent results. Future studies are required to establish if uric acid can be used as a biomarker for risk assessment and/or as a novel therapeutic target in SLE.

One-year renal outcome in lupus nephritis patients with acute kidney injury: a nomogram model.

To develop a short-term renal outcome prediction model for acute kidney injury (AKI) in patients with LN. Two lupus AKI cohorts from two independent centres during 2013-2019 were included: a derivation cohort from a rheumatology centre and a validation cohort from a nephrology centre. Clinical characteristics and renal histologic features were obtained. The outcome measurement was the recovery of kidney function within 12 months. Lasso regression was used for feature selection. Prediction models with or without pathology were built and a nomogram was plotted. Model evaluation including calibration curve and decision curve analysis was performed. A total of 130 patients were included in the derivation cohort and 96 patients in the validation cohort, of which 82 and 73 patients received a renal biopsy, respectively. The prognostic nomogram model without pathology included determinants of SLE duration, days from AKI onset to treatment and baseline creatinine level [C-index 0.85 (95% CI 0.78, 0.91) and 0.79 (95% CI 0.70, 0.88) for the two cohorts]. A combination of histologic tubulointerstitial (TI) fibrosis in the nomogram gave an incremental predictive performance (C-index 0.93 vs 0.85; P = 0.039) in the derivation cohort but failed to improve the performance in the validation cohort (C-index 0.81 vs 0.79; P = 0.78). Decision curve analysis suggested clinical benefit of the prediction models. The predictive nomogram models might facilitate more accurate management for lupus patients with AKI.

Good pregnancy outcomes in lupus nephritis patients with complete renal remission.

The aim of this study was to investigate pregnancy outcomes and risk factors in patients with lupus nephritis (LN). A total of 158 pregnancies in 155 women with LN were divided into a remission group and a control group according to whether they achieved complete renal remission (CRR) prior to pregnancy. The adverse pregnancy outcomes and risk factors were retrospectively analyzed. In the remission group, 130 LN patients with 133 pregnancies (two twin pregnancies) delivered 127 live births; 25 LN patients with 25 pregnancies delivered 19 live births in the control group. Compared with the control group, the remission group had significantly lower incidence of LN relapse, fetal loss and premature birth. For LN patients in the remission group, a CRR duration <18 months [odds ratio (OR) 11.24, 95% confidence interval (CI) 2.95-42.80, P <0.001] and anti-C1q antibody positivity before pregnancy (OR 7.2, 95% CI 1.38-37.41, P=0.019) were independent risk factors for LN relapse; anti-phospholipid antibody positivity (OR 9.32, 95% CI 1.27-68.27, P=0.028) and prednisone dosage during pregnancy≥12.5mg/day (OR 3.88, 95% CI 1.37-10.99, P=0.011) were independent risk factors for fetal loss and premature birth, respectively; and age >30 years was an independent risk factor for preeclampsia and premature birth. LN patients with a CRR duration greater than 18 months were associated with good pregnancy outcomes and lower LN relapse. Age, anti-C1q and anti-phospholipid antibodies, and prednisone dosage during pregnancy were risk factors for adverse pregnancy outcomes.

Prognostic significance of hypertension at the onset of lupus nephritis in Chinese patients: prevalence and clinical outcomes.

The demographic features, and clinical and histological characteristics of lupus nephritis (LN) patients with hypertension in the Chinese population remain unclear. Hence, the clinical characteristics of LN with and without hypertension were retrospectively analyzed. A total of 764 LN patients (53.1%) were hypertensive. These hypertensive patients had higher levels of serum creatinine and blood urea nitrogen, and lower estimated glomerular filtration rates, when compared to their normotensive counterparts (P < 0.05). Furthermore, these hypertensive patients had higher median acuity index and chronicity index scores, when compared to normotensives (P < 0.001). In terms of histology, hypertensive patients were more likely to develop glomerular sclerosis, thickened glomerular capillary loops, or crescent formations, and had more severe endothelial cell proliferation, when compared to normotensive patients (P < 0.001). Hypertensive patients also had a higher percentage for more severe tubular atrophy, interstitial inflammatory cell infiltration and interstitial fibrosis (P < 0.001). Compared with normotensive patients, hypertensive patients exhibited a significant decline in survival time and rate for all end points (P < 0.01). The presence of hypertension was an independent predictor of mortality (P = 0.009), ESRD (P = 0.026), and doubling of serum creatinine (P = 0.017). In conclusion, hypertension is associated with poor clinical and renal outcome in LN patients. The monitoring and control of hypertension should be considered an important clinical goal in the treatment of LN patients.

Circulating anti-C3b IgG in lupus nephritis: A large cohort study

The current study aimed to analyze the clinical significance and bio-functional properties of anti-C3b IgG based on a lupus nephritis cohort. We found that the prevalence of anti-C3b IgG in our cohort was 47.8%. Patients with positive anti-C3b IgG had significantly higher SLEDAI, lower circulating C3 and C4 levels. Anti-C3b IgG levels were positively correlated with C3 or C1q deposition in kidneys and several active pathological lesions. The positivity of anti-C3b IgG was an independent risk factor for the composite endpoints in the subgroup of proliferative lupus nephritis patients. In vitro, the purified IgG fractions from positive patients resulted in increased C3a generation through the alternative pathway, and interfered factor H and CR1 binding to C3b. Our findings indicated that anti-C3b IgG associated with local renal injury and long-term outcomes in lupus nephritis patients, possibly through leading to the complement alternative pathway over-activation.

Clinical and histopathological features and short-term outcomes of lupus nephritis: a prospective study of 100 Egyptian patients.

The short-term outcomes of lupus nephritis (LN) are variable and unpredictable among individuals. We aimed to evaluate the clinical and histopathological features and short-term renal outcomes in LN patients. This was a prospective cohort study carried out at nephrology and rheumatology units in Egypt between 2018 and 2019. A total of 100 patients with biopsy-proven LN were studied. Patients were evaluated for response after six months. The female-to-male ratio was 8.1:1. About 70% of patients were hypertensive at disease onset, with rates for classes I, II, III, IV, V and VI LN being 1%, 7%, 20%, 53%, 14% and 6%, respectively. Among the immunosuppressive drugs used for induction, mycophenolate mofetil (MMF) represented the most commonly used (44%) followed by cyclophosphamide (CYC; 37%). After six months of follow-up, about two thirds of patients achieved remission. There was no significant difference in remission rate between MMF and CYC. On multivariate analysis, serum creatinine (SCr) at presentation was the most significant predictor of renal recovery. According to the receiver operating characteristic curve, the cut-off value of SCr was 1.6 mg/dL, with a sensitivity of 76% and specificity of 71% predicting renal recovery. Repeat renal biopsy was needed in 10 patients; class and treatment strategy changed in 40% and 70% of them, respectively. Our findings in Egyptian LN patients compare favourably with most studies.

Cryptococcal meningitis in patients with lupus nephritis.

Cryptococcal meningitis (CM) is a rare condition in patients with lupus nephritis (LN). Here, we describe the clinical characteristics, possible risk factors, and outcomes of LN patients with CM. A systematic review of medical records from16 LN patients with CM admitted to our hospital was performed. A total of 32 cases were randomly selected as controls from LN patients without infection during the same period. The mean age of patients with CM at presentation was 35.1 years, and the female-to-male ratio was 15:1.The most common clinical manifestation was headache (93.7%); patients with CM had a significantly higher prednisone dose at the time of hospitalization, a higher SLE Disease Activity Index (SLEDAI), a higher urine protein/creatinine ratio, and a lower CD4+ T cells count than those without infection (p < 0.05). Patients with CM also had significantly higher activity index and more moderate and severe mesangial proliferation than those without infections (p < 0.001 and p = 0.025, respectively). Serious renal pathological changes, mass proteinuria, higher SLEDAI, higher prednisone dose, and a decline in CD4+ T cells could be risk factors for CM in patients with LN. Key Points ⦁ LN patients with CM had more serious renal pathological changes than those without infections; serious renal pathological changes could be a major risk factor for CM in patients with LN.

Long-Term Clinical Outcomes of Lupus Nephritis Patients Undergoing Peritoneal Dialysis: A Matched, Case-Control Study.

The long-term clinical outcomes of peritoneal dialysis (PD) for patients with lupus nephritis (LN) have not been well researched. In the present study, we investigated the long-term prognosis of a Chinese PD cohort. This was a retrospective case-control study that included LN patients receiving PD treatment for more than 90 days from January 2006 to December 2012. Non-diabetic control patients were selected using a ratio of 1:2 for age- and gender-matching. The primary outcome was all-cause mortality. Secondary outcomes included technique failure and hospitalization rate. All patients were followed up to 31 December 2017. A total of 28 LN patients on PD (89.3% female, mean age 42.2±15.8 years) and 56 controls were included. After a median follow-up period of 53.1 months, 11 LN patients died. The cumulative 1-, 3-, and 5-year patient survival rates were 92.4%, 84.7%, and 67.6% in LN patients, and 100%, 93.5%, and 82.9% in the control group, respectively (p = 0.035). After adjusting for confounders, LN was not significantly associated with mortality (hazard ratio [HR]: 1.39, 95% confidence interval [CI]: 0.45 - 4.26); However, LN was still an independent risk factor of technique failure (HR: 2.87, 95% CI: 1.08 - 7.66). Meanwhile, the LN group had significantly higher hospitalization and infection rates. In conclusion, LN patients undergoing PD had poor patient survival and technique survival, and higher hospitalization and infection rates.

A five consecutive years' study of renal function outcome among biopsy proven lupus nephritis patients in Southern Iran.

Introduction Lupus nephritis (LN) is one of the most common complications of systemic lupus erythematous (SLE) responsible for an increase in mortality and morbidity. This study was conducted to evaluate the outcome for LN patients and factors that correlate with their outcome. Materials and methods We included 80 patients with proved LN and more than three-years follow up at Shiraz University of Medical Sciences. We prepared a data gathering sheet for each patient and extracted the data from patients' file records which existed in the hospital. Results The mean age of patients was 36.6 ± 10.6 years, and 88.3% of patients were women. Men develop remission less than women (three men (33.3%) vs 49 women (72.1%), p = 0.014). Chronic kidney disease (GFR < 60) developed in 14.2% of our patients, and 7.8% progressed to end stage renal disease (ESRD). We found a significant relation between initial creatinine (Cr), GFR, and urine 24 hour protein with developing ESRD ( p = 0.002, 0.039, < 0.001, respectively). Also we found that hypertensive patients are at risk of developing ESRD 0.4 times more than normotensive patients ( p = 0.047, CI: 0.131-0.985). Lack of remission was significantly associated with ESRD progression ( p = 0.025). Conclusion There is a strong agreement among studies that initial Cr, hypertension and lack of remission are associated with poor outcome in LN patients. As a result we must observe hypertensive patients and patients with increased Cr more carefully. Also, we should consider changing treatment in patients who do not develop remission. In spite of dominancy of women in SLE, men are likely to have poorer outcomes.

Downregulation of the phosphatase JKAP/DUSP22 in T cells as a potential new biomarker of systemic lupus erythematosus nephritis.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease that is characterized by systemic inflammation and multiple organ failures. Dysregulation of T cells plays a critical role in SLE pathogenesis. Our previous study indicates that JKAP (also named DUSP22) inhibits T-cell activation and that JKAP knockout mice develop spontaneous autoimmunity; therefore, we investigated whether JKAP downregulation is involved in SLE patients. JKAP protein levels in purified T cells were examined by immunoblotting using blood samples from 43 SLE patients and 32 healthy controls. SLE patients showed significantly decreased JKAP protein levels in peripheral blood T cells compared to healthy controls. JKAP protein levels in peripheral blood T cells were inversely correlated with SLE disease activity index (SLEDAI) and anti-dsDNA antibody levels. JKAP downregulation in T cells was highly correlated with daily urinary protein amounts and with poor renal outcome in lupus nephritis patients. Notably, the diagnostic power of JKAP downregulation in T cells for active lupus nephritis was higher than those of serum anti-dsDNA antibody, C3, and C4 levels. Moreover, T-cell-specific transgenic mice expressing a dominant-negative JKAP mutant developed spontaneous autoimmune nephritis. Furthermore, JKAP-deficient T cells overproduced complement components, soluble ICAM-1, and soluble VCAM-1 in the kidney; these cytokines have been reported to be involved in lupus nephritis. Taken together, JKAP downregulation in T cells is a novel diagnostic and prognostic biomarker for SLE nephritis.

Clinical outcomes of lupus nephritis patients with different proportions of crescents.

The prognostic significance of different proportions of crescents in lupus nephritis (LN) remains unclear. We assessed the long-term prognosis of LN patients with different proportions of crescents. In this single-center, retrospective cohort study, 788 eligible LN patients were enrolled. The primary endpoint was doubling of baseline serum creatinine and end-stage renal disease; the secondary endpoint was death. There were 406 (51.5%) patients demonstrating crescents at biopsy, and they had more severe baseline status: lower estimated glomerular filtration rate (eGFR), more proteinuria, more severe microscopic hematuria, and higher pathological scores for both activity index (AI) and chronicity index (CIn) (all p < 0.001, respectively). After a median follow-up period of 56 months (range: 3-172 months), no significant differences were observed in terms of renal or patient survival in these two groups (p = 0.188). In LN patients with crescents, patient survival was poorer along with the increase in the proportion of crescents; for crescentic LN, patient survival was 78.9% at five years and 52.6% at 10 years (vs. subgroups of crescent proportion <10%, 10%-19%, 20%-49%: 95.5%, 92.3%, 91.7% at five years; 86.1%, 80.1%, 66.5% at 10 years, respectively, p = 0.008). Furthermore, there were higher proportions of crescents independently predicted for adverse outcomes of renal progression and mortality (p = 0.049) after adjusting for age, sex, baseline eGFR, proteinuria, AI, and CIn in the multivariate Cox proportional hazard model. The overall long-term renal survival of LN patients with and without crescents was comparable. However, a higher proportion of crescents increased the risk for unfavorable outcomes. Therefore, more attention should be paid to the lesions of crescents, and more prospective studies are needed to explore the optimal regimens for LN patients with different proportions of crescents.

Plasmapheresis Is Associated With Better Renal Outcomes in Lupus Nephritis Patients With Thrombotic Microangiopathy

The aim of this study was to evaluate the efficacy of plasmapheresis in patients with lupus nephritis-combined thrombotic microangiopathy (TMA) in a Chinese cohort.Clinical and therapeutic data of patients with lupus nephritis-combined TMA were collected retrospectively. A comparison between those with and without plasmapheresis was performed.Seventy patients with renal biopsy-proven TMA in lupus nephritis were treated with conventional combined corticosteroid and immunosuppressive agents as induction therapy, 9 of the 70 patients received additional plasmapheresis. The plasmapheresis group presented with more severe SLE and renal activity indices, including a significant higher ratio of neurologic disorder (P = 0.025), lower level of platelet count (P = 0.009), higher value of serum creatinine (P = 0.038), higher percentage of anti-cardiolipin antibodies positive (P = 0.001), and higher Systemic Lupus Erythematosus Disease Activity Index scores (P = 0.012), than that of the nonplasmapheresis group. However, the plasmapheresis group had a significant higher rate of remission and a lower ratio of treatment failure than that of the nonplasmapheresis group (P = 0.03). As the baseline data were significantly different between the 2 groups, the propensity score match was further designed to avoid retrospective bias. After re-analysis, the plasmapheresis group still had a significant higher rate of remission and a lower ratio of treatment failure than that of the nonplasmapheresis group (P = 0.018). More importantly, the plasmapheresis group had significant less composite endpoints than that of the nonplasmapheresis group (P = 0.005).Our study suggested that additional plasmapheresis on conventional induction therapy may benefit patients with lupus nephritis-combined TMA, which warrants further explorations.

Clinicopathologic Characteristics and Outcomes of Lupus Nephritis With Antineutrophil Cytoplasmic Antibody: A Retrospective Study.

Few studies have analyzed the clinicopathologic characteristics and outcomes of lupus nephritis (LN) patients with antineutrophil cytoplasmic antibody (ANCA).The clinical and renal histopathologic data of 154 patients with biopsy-proven LN from 2011 to 2013 were analyzed retrospectively. The patients were followed up for a median period of 16.8 ± 9.4 months, and their outcomes were analyzed. Multivariate Cox analysis was used to evaluate the independent factors for poor outcomes.Among the 154 LN patients, 26 (16.88%) were seropositive for ANCA. The incidences of alopecia, oral ulcer, photosensitivity and skin lesion, and psychosomatic manifestations in the ANCA-positive group were significantly higher than in the ANCA-negative group (P = 0.007, 0.02, 0.02, and 0.03, respectively). Compared with the ANCA-negative group, the ANCA-positive group had significantly lower levels of complement C3 (P = 0.03). Additionally, the positive rate of antinucleosome antibodies, antihistone antibodies, antimitochondrial antibody M2, and anticardiolipin antibodies were higher significantly in the ANCA-positive patients than in the ANCA-negative patients (P = 0.001, 0.001, 0.03, 0.005, respectively). The ANCA-positive group had a notably higher chronic index than the ANCA-negative group (P = 0.01). During the follow-up, the complete remission rate in the ANCA-negative group was higher than that in the ANCA-positive group (P = 0.01). The cumulative renal survival rate in the ANCA-positive group was significantly lower than in the ANCA-negative group (log-rank = 6.59, P = 0.01). Multivariate Cox analysis revealed that the reduced estimated glomerular filtration rate (HR, 1.02; 95% confidence interval, 1.01 to 1.03; P = 0.005), NLR (HR, 1.20; 95% confidence interval, 1.02 to 1.40; P = 0.03), and ANCA (HR, 3.37; 95% confidence interval, 1.12 to 10.09; P = 0.03) were independent risk factors for patients’ renal survival after adjusting for age, sex, crescent formation, and glomerulosclerosis.The study found ANCA in LN patients is not rare, and patients with ANCA present with more severe clinicopathologic injuries. Thus, ANCA is an independent risk factor for poor renal outcomes in LN patients.

Clinical Outcomes of Lupus Nephritis Patients with Different Proportions of Crescents

Clinical Outcomes of Lupus Nephritis Patients with Different Proportions of Crescents

The GSTA1 polymorphism and cyclophosphamide therapy outcomes in lupus nephritis patients

Pulsed low-dose cyclophosphamide (CTX) therapy has become a very effective approach in improving the clinical outcomes of lupus nephritis (LN) patients. However, variations of CTX therapeutic outcomes in LN patients are incompletely understood. We investigated the contributions of known allelic variants to CTX therapy outcomes in 77 LN patients. Then, 22 out of the 77 patients were randomly enrolled to evaluate the pharmacokinetic profiles. LN patients with a GSTA1*A mutation (CT heterozygous) had more risk of non-remission (44% vs. 20%, P=0.005). Pharmacokinetic data indicated that patients with a GSTA1*A heterozygous variant had a lower exposure to 4-hydroxycyclophosphamide (4OHCTX) compared to wild-type patients (AUC4OHCTX: 12.8 (9.8, 19.5) vs. 27.5 (18.1, 32.8) h mg/l, P=0.023). Clinical remission was significantly related to higher exposure of 4OHCTX (P=0.038). In conclusion, LN patients with GSTA1*A heterozygous genotypes had poor CTX treatment remission due to less exposure to activated metabolites of CTX.

High collagen I gene expression as an independent predictor of adverse renal outcomes in lupus nephritis patients with preserved renal function.

The deposition of extracellular matrix is a major pathogenic mechanism leading to fibrosis and progressive decline in renal function in patients with lupus nephritis (LN). Currently, available clinicopathologic features cannot predict renal outcome consistently. To test that the expression of renal fibrogenic genes correlates with renal fibrosis at the time of biopsy and is predictive of renal outcomes. Renal gene expression levels of transforming growth factor β-1 (TGFB1), and collagen I (COL1) were studied by real-time multiplex quantitative polymerase chain reaction in a prospective cohort of patients with LN (n = 39). Extracellular matrix index (ECMI) and collagen I/III matrix index were measured from Picro-Sirius Red-stained slides under normal and polarized light, respectively. After follow-up (median, 43.9 months), renal failure (50% reduction in glomerular filtration rate [GFR] or dialysis) had developed in 13 subjects. The expression levels of renal fibrogenic genes were increased as compared to controls without LN. COL1 correlated with collagen I/III matrix index at baseline. Both high expression of TGFB1 or COL1 tended to predict renal failure by univariate analysis. By multivariate analysis, high ECMI and low GFR were predictive of renal failure. In patients with baseline GFR of 60 mL/min/1.73 m(2) or greater, high renal COL1 expression was an independent (hazard ratio = 4.4, P = .04) predictor of renal failure. High renal COL1 expression is a strong predictor of adverse renal outcome in patients with LN and preserved baseline GFR. These findings support larger prospective studies to confirm the benefits of COL1 in identifying patients at high risk of progression to renal disease.