Silent Lupus Nephritis Research Articles

Risk factors and prognosis of pediatric silent lupus nephritis with class Ⅲ to Ⅴ

To study the risk factors and prognostic characteristics of pediatric silent lupus nephritis (SLN) with class Ⅲ to V. A retrospective study was conducted to collect clinical data from 30 children diagnosed with SLN at the Department of Pediatrics, Second Xiangya Hospital, Central South University, from May 2007 to April 2023. Based on renal pathological classification, the patients were divided into a class Ⅱ group (12 cases) and a class Ⅲ to Ⅴ group (18 cases). The risk factors for the occurrence of class Ⅲ to Ⅴ SLN were analyzed, and the prognostic characteristics were summarized. Among the 30 SLN patients, the median follow-up time was 61.50 months. There were no statistically significant differences in the proportions of patients who discontinued glucocorticoids or achieved low disease activity status, nor in the annual decline rate of estimated glomerular filtration rate (eGFR) between the class Ⅱ and class Ⅲ to V groups (P>0.05). However, three patients in the class Ⅱ group progressed to stage 1 chronic kidney disease (CKD), while eight patients in the class III to V group reached stage 1 CKD, and four patients reached stage 2 CKD. Among the 26 female SLN patients, serum complement C3 levels in the class III to V group were lower than those in the class Ⅱ group (P<0.05). Serum C3 levels in SLN patients, as well as in female SLN patients, were negatively correlated with the fluorescence intensity of IgA, IgG, and C3 immune complexes in the kidneys (P<0.05). Additionally, serum C3 levels in female SLN patients were negatively correlated with the renal pathological activity index (P<0.05). Binary logistic regression analysis indicated that being female and having low serum complement C3 levels were risk factors for the occurrence of class Ⅲ to V SLN in children (P<0.05). Class Ⅲ to V SLN is not uncommon among SLN children, and there remains a risk of long-term renal function progression. Being female and having low serum complement C3 levels are identified as risk factors for class Ⅲ to V SLN in children.

Clinical profiles in pediatric systemic lupus erythematosus: a retrospective study

Aims: This study aimed to analyse clinical and laboratory findings, prognosis, and survival of systemic lupus erythematosus (SLE) patients, differentiating according to gender, pubertal status, and renal involvement. Methods: Ninety-six pediatric SLE patients, diagnosed using ACR criteria, were retrospectively analyzed. Inclusion criteria comprised age under 18, meeting at least four ACR criteria, and six months of monitoring. Data encompassed demographics, symptoms, diagnosis, organ involvement, autoantibodies, treatment, prognosis, and survival. Categorization was based on gender and pubertal status. Renal biopsies followed WHO-ISN classification, with asymptomatic findings termed “silent lupus nephritis.” Biopsied patients were divided into proliferative and non-proliferative lupus nephritis categories, excluding irreversible damage cases. Outcomes studied included remission, relapse, end-stage renal failure, and mortality. Results: Among 96 participants, females constituted 82.3%, males 17.7%, resulting in a female-to-male ratio of 4.6:1. Mean age at diagnosis was 11.9 years, with 37 prepubertal (38.5%) and 59 pubertal (61.5%) cases. Oral-nasal ulcers (p=0.01) were more prevalent in males related to system involvement. Nephrotic syndrome prevalence increased from 21.6% in prepubertal to 44.1% in pubertal cases (p=0.025). Positive Anticardiolipin IgM antibodies decreased from 56.2% in prepubertal to 25.9% in pubertal cases (p=0.047). Type IV lupus nephritis was predominant, followed by Type II, in prepubertal and pubertal groups and both genders. Proliferative lupus nephritis showed higher rates of renal involvement (95.7% vs. 65.6%), nephrotic syndrome (46.8% vs. 21.9%), proteinuria (89.4% vs. 62.5%), hematuria (57.4% vs. 28.1%), elevated creatinine (43.5% vs. 9.7%), and low albumin (67.4% vs. 23.3%). Cases with proliferative lupus nephritis had higher neuropsychiatric involvement (36.2% vs. 12.5%), seizures (25.5% vs. 3.1%, p=0.008), and increased hemolytic anemia rates (78.7% vs. 56.2%, p=0.033). Thirteen had silent lupus nephritis, revealing various types through biopsy. All reported deaths occurred within the first five years, resulting in stable 91% survival rates at 5, 10, and 15 years. Conclusion: This study provides insights into the clinical, prognostic, and survival characteristics of pediatric systemic lupus erythematosus (SLE), revealing notable patterns related to gender, pubertal development, and renal involvement. There is an association between proliferative lupus nephritis and renal involvement, nephrotic syndrome, and neuropsychiatric symptoms. Significantly, silent lupus nephritis highlights the complex renal implications, necessitating diligent surveillance for prompt intervention.

Silent Lupus Nephritis: Renal Histopathological Profile and Early Detection with Urinary Monocyte Chemotactic Protein 1.

ObjectiveLupus nephritis (LN) affects almost half of all individuals with systemic lupus erythematosus (SLE). Overt LN (OLN) symptoms might vary from asymptomatic microscopic hematuria to renal failure. However, when there are no clinical or laboratory indicators of renal involvement, some people with silent LN (SLN) may have pathological evidence of renal involvement identified by renal biopsy. Monocyte Chemotactic Protein 1 (MCP-1) is a chemotactic factor that promotes leukocyte migration to the kidney. MCP-1 urine levels (uMCP-1) have been demonstrated to be high in individuals with active LN. The purpose of this study was to discover the occurrence of SLN, as well as the possible variations between overt LN (OLN) and SLN across SLE patients based on the histopathological assessment, as well as the role of uMCP-1 in the early detection of SLN.MethodsAn overall of 144 patients with SLE were included in the current research. Patients were subsequently divided into two groups: individuals who did not have clinical evidence of LN (84 patients) and those with OLN (60 patients). All the patients were subjected to the following investigations: uMCP-1, erythrocyte sedimentation rate (ESR), complement C3 (C3), complement C4 (C4), creatinine, albumin/creatinine ratio (uACR), creatinine clearance, quantitative assessment of proteinuria by 24-hour urine proteinuria (24hr UP) and percutaneous renal biopsy.ResultsSixty patients from group I (71.4%) showed glomerular lesions on renal biopsy (SLN), and class II was the predominant class. uMCP-1 had a sensitivity of 95.2% and a specificity of 98% in the detection of SLN, and uMCP-1 values were markedly higher in patients with OLN in comparison to SLN.ConclusionThe actual frequency of SLN may be higher than expected. High levels of uMCP-1 may have warranted the early activity of LN. uMCP-1 can be used as a non-invasive, useful tool for the prediction of LN.

Retrospective review of the clinical and laboratory data in silent lupus nephritis.

To determine the ratio of renal disease necessitating immunosuppressive treatment in lupus patients who are clinically asymptomatic by means of renal disease. It was also examined whether silent lupus nephritis is associated with any of the non-renal clinical findings. All kidney biopsies performed in lupus patients between 1990 and 2009 at the Rheumatology Department of Ege University Faculty of Medicine were retrospectively screened. Among the 258 kidney biopsies screened, 54 had no clinical renal findings but had active disease together with anti-dsDNA positivity and/or hypocomplementemia. Patients were classified into two groups who require and do not require immunosuppressive therapy according to their final pathological results at biopsy. The frequency of serious renal involvement in the sample was calculated. Then subgroups were compared with each other in terms of the clinical and laboratory features using Statistical Package for Social Sciences version 13 software. Thirteen of the 54 patients (24%) had severe renal involvement requiring immunosuppressant therapy. When the groups were compared to each other, it was found that serositis and hematologic involvement were significantly more frequent in patients who needed immunosuppressive treatment (42.9% versus 10.0%; p = 0.003 and 64.3% versus 37.5; p = 0.039). Even in the absence of clinical renal manifestations, active patients at high risk of renal disease such as hypocomplementemia, anti-ds DNA positivity may have severe renal disease requiring immunosuppressive treatment. Thus, renal biopsy indications in lupus patients should better be revaluated.

RENAL HISTOPATHOLOGICAL PROFILE IN PATIENTS WITH SILENT LUPUS NEPHRITIS

Background: Silent lupus nephritis (SLN) is a life menacing consequence of systemic lupus erythematous (SLE). This condition is characterized by pathological impairment of the kidney in the obscurity of clinical or laboratory manifestations. Objective: To reveal the existence of SLN along with the potential differences between overt lupus nephritis (OLN) and SLN among a sample of Egyptian patients based on histopathological assessment. Patients and Methods: It is a prospective case-control study which was performed at nephrology units, internal medicine department, Elhussein and Sayed Galal university hospitals, faculty of medicine, Al-Azhar University, Cairo, Egypt, throughout the entire period April 2016 to November 2019. Patients aged more than 18 years (216 months) and fulfilled at least 4 of the American College of Rheumatology criteria for the classification of systemic lupus erythematosus (SLE) were enrolled in the current study. Patients were further assorted into two groups; patients with SLN and those with OLN. Patients were subjected to the following investigations: 1.Complete blood count, using Coulter counter Max-M (Coulter Cooperation, Florida, USA) 2.Erythrocyte sedimentation rate, (Wester green method) (Ref: < 20mm/hr) 3.S. Albumin, S. Creatinine. Albumin/Creatinine ratio. Creatinine clearanc & eGFR using the Modification of Diet in Renal Disease (MDRD) formula. 4. Liver function tests. 5. Coagulation profile. 6. Urine analysis (Fresh morning midstream urine) to exclude infection. 7. Quantitative assessment of proteinuria by Pr/creat. Ratio (Ref. <0.2). Assessment of auto-antibodies and complement system: Autoantibodies to ds-DNA, RNP. SSA, SSB, Sm and Scl-70, C4 and C3 serum levels were assessed in all of the included patients. In particular, the titer of anti-dsDNA antibodies was evaluated by enzyme- Radiological evaluation: Patients were subjected to pelvi-abdominal ultrasound in order to obtain valuable data about the morphological appearance of the kidney and to detect any urological abnormality. Renal biopsy: Percutaneous renal biopsy was carried out under local anesthesia. Results: An overall 40 patients with SLE who developed lupus nephritis were enrolled in the current study. Among them, 20 patients had OLN, whereas 20 patients were SLN. Based on ISN/RPS Classification, stage II was the predominant stage, 13 patients, among patients with SLN, whilst stage V was the predominant stage among the OLN patients. Additionally, five and three patients were stage III among the SLN and OLN groups, respectively. Furthermore, the presence of RBCs Cast (r=0.479, P=0.032) in urine and decreased levels of complement (r=0.676, P=0.001) showed a statistically significant positive correlation with the high grades of lupus nephritis among SLN group. Conclusion: Patients with SLE should be subjected to close follow up evaluation and renal biopsy for early detection of SLN to determine the activity, severity, and chronicity of LN.

Interleukin-34 as a marker for subclinical proliferative lupus nephritis.

Background Lupus nephritis (LN) is an ominous manifestation of systemic lupus erythematosus (SLE). Clinical renal affection is present in about 70% of lupus patients, and more patients have histological evidence of renal involvement without clinical manifestations. This study aimed to investigate the potential role of serum interleukin-34 (IL-34) as an early marker for the detection of silent LN. Methods Thirty-three lupus patients with silent LN (group I), 37 patients with clinical LN (group II) and 20 controls were included. The SLE Disease Activity Index (SLEDAI), IL-34, anti-dsDNA antibodies and renal biopsy were assessed in all patients. Results Serum IL-34 levels were significantly higher in all lupus patients compared to healthy controls ( p &lt; 0.001) and showed a significant positive correlation with SLEDAI score. SLE patients with positive anti-dsDNA antibodies had more active disease according to SLEDAI and higher levels of IL-34 than those with negative anti-dsDNA antibodies. In both studied groups, serum IL-34 levels were significantly higher in patients with proliferative LN (class III and class IV) than those with non-proliferative lupus (class II and class V) and controls. Yet, in both groups, IL-34 was not useful in differentiating active from chronic renal affection. Conclusion In lupus patients with insignificant proteinuria, serum levels of IL-34 distinguished the different histological classes of subclinical LN. Serum IL-34 may be used as a surrogate marker for early renal affection in silent LN, especially the proliferative type.

Treatable renal disease in children with silent lupus nephritis detected by baseline biopsy: association with serum C3 levels.

Lupus nephritis is identified in up to 75% of patients with juvenile systemic lupus erythematosus and may present with abnormal urinary findings (overt lupus nephritis) or be apparent only upon renal biopsy (silent lupus nephritis). We investigated whether serum complement levels correlate with renal pathology in pediatric patients with silent lupus nephritis. We performed baseline renal biopsy in 45 children diagnosed with juvenile systemic lupus erythematosus who were admitted to Kagoshima University Hospital between January 2000 and June 2015. Patients were classified as having overt or silent lupus nephritis based on urinary findings at renal biopsy. Silent lupus nephritis was identified in 55.5% (25/45) of cases. Of these, 6 (13.3%) were classified as class III nephritis, according to the International Society of Nephrology/Renal Pathology Society criteria. Decreased serum C3 levels were associated with the renal pathology classification for patients with silent but not with overt lupus nephritis. No differences in serum C4 levels were identified between cases of silent and overt lupus nephritis. Baseline renal biopsy is a critical component of the work-up of juvenile systemic lupus erythematosus as treatable renal pathology may be present in the absence of urinary signs. Serum C3 may be an important marker of the progression of silent lupus nephritis.

Interleukin-17 - association to silent lupus nephritis and disease activity

Background: Systemic lupus erythematosus is a multiorganic, chronic immune disease and lupus nephritis, a severe manifestation, represents the strongest predictor of a poor outcome of this pathology. Cytokines play an important role in lupus nephritis and consequently, their use as biomarkers of active systemic lupus erythematosus disease is of particular interest. The purpose of this work was to study the pro-inflammatory role of interleukin-17 in renal involvement in patients with systemic lupus erythematosus (SLE). Methods: We performed a retrospective study of 87 patients diagnosed with SLE according to the Systemic Lupus International Collaborating Clinics 2012 diagnosis criteria. In this study, we determined the serum levels of interleukin-17 by ELISA. Results: It was observed that 49 patients in the study group presented with positive values of interleukin-17, range (1.12 - 23.66) pg/ml. There was a positive correlation of interleukin-17 with active SLE as assessed by the Systemic Lupus Erythematous Disease Activity Index. No association was found between serum interleukin-17 level and renal pathology at the inclusion or in the clinical history of the patients. Patients with leukocyturia and hematuria presented higher values of serum interleukin-17 than those without these manifestations. In the linear regression model, after adjusting for age, gender and treatment we found an independent association between serum IL-17 levels and leukocyturia presence with OR=2.06, 95% CI range (1.22-2.89). Conclusions: A positive correlation has been observed between serum IL-17 and the SLE disease activity as assessed by the SLEDAI score computed without anti-DNA antibodies. Also, the IL-17 levels was strongly associated with the presence of leukocyturia and hematuria, even in patients with no clinical evidence of renal disease that might have silent lupus nephritis usually associated with a benign renal outcome.

An Unusual Initial Presentation of Lupus Nephritis as a Renal Mass

Lupus nephritis is a frequent manifestation of systemic lupus erythematous. Lupus nephritis usually presents with abnormal urinalysis, proteinuria, and/or renal insufficiency. We report a case of a 48-year-old woman who underwent partial nephrectomy for a fortuitously discovered solid enhancing left kidney mass. No neoplastic cells were found in the biopsy specimen; however, the pathology findings were compatible with immune complex glomerulonephritis with a predominantly membranous distribution, a pattern suggestive of lupus nephritis. The mass effect was apparently due to a dense interstitial lymphocytic infiltrate resulting in a pseudotumor. Further investigation revealed microscopic hematuria with a normal kidney function and no significant proteinuria. Antinuclear antibodies were negative, although anti-DNA and anti-SSA/Rho antibodies were positive. A diagnosis of probable silent lupus nephritis was made and the patient was followed up without immunosuppressive treatment. After two years of follow-up, she did not progress to overt disease. To our knowledge, this represents the first case of lupus nephritis with an initial presentation as a renal mass.

AB0536 Renal Biopsy in Patients with Systemic Lupus Erythematosus and Proteinuria Less than 0.5 G/24Hrs

BackgroundThe currently indications for a first renal biopsy in patients with systemic lupus erythematosus (SLE) are the presence of a confirmed 24 hours urinary proteins ≥0.5 g, an active urinary...

AB0425 Silent lupus nephritis in protocol biopsy after complete remission

BackgroundRenal biopsy is an essential tool in lupus nephritis (LN) diagnose, It is also useful to establish prognosis. In general biological markers as complement, Anti ADN autoantibody are used to...

Nefropatía lúpica silente

Silent lupus nephritis (SLN) is an unusual clinical presentation of lupus nephritis (LN) and may be an underdiagnosed entity. Renal biopsy is the only diagnostic method but is invasive and is not indicated in asymptomatic patients. Consequently, the prevalence of this disease is difficult to determine. Data from more than 250 SLN cases published in the literature were analyzed from isolated cases, case studies and prospective studies. Of the 226 well-described cases, we selected 197 reported after the 1970s. Patients with class I lesions (n=29, 15%) were excluded as they fell outside the definition of SLN. Among included patients, there were 107 with class II (54.3), 45 with class III (22.8%), 50 with class IV (25.4%), 9 with class V (4.6%) and one with class VI. Forty percent had proliferative forms (classes III and IV), the most severe forms of LN.Of the 197 patients, 65 patients (33%) from six publications were followed-up. The data did not allow conclusions to be drawn on the epidemiology or prognosis of this entity. Future studies are required to clarify these issues.

Further description of early clinically silent lupus nephritis

Thirty silent lupus nephritis (SLN) patients were compared to 16 individuals bearing overt lupus nephritis (OLN). Results included: years of systemic lupus erythematosus (SLE) diagnosis were significantly earlier (4.6 +/- 2.8 years) in SLN than in OLN (7.18 +/- 3.61) (P < 0.05). Neurological compromise, hypertension, normocitic anemia and lymphopenia were significantly prevalent in OLN than in SLN (P < 0.05). Beside normal urinary sediment and renal function tests, the SLN group showed a moderate increase of both activity (AI) and chronicity (CI) renal pathology index when compared to highly increased AI and CI in OLN (P < 0.05). Seventy percent of SLN patients were ISN/RPS Classes I (6.6%) and II (63.3%) while 81% of OLN cases were Classes III, IV (37.5%) and V. IgG, IgA, IgM, lambda chain, C3 and fibrinogen immune deposits were found in 90% or over in both SLN and OLN individuals while in 60% or over, both groups also showed kappa chain, Clq and C4 deposits. While prevalence of ANA, anti-dsDNA and anti-C1q antibodies were similar in both groups, anti-histone, anti-RNP, CIC and CH50 serum levels were significantly different in OLN versus SLN (P < 0.05). We strongly suggest that indeed SLN is the earliest stage in the natural history of lupus nephritis.

F.52. Further Description of Early Clinically Silent Lupus Nephritis

F.52. Further Description of Early Clinically Silent Lupus Nephritis

Renal Outcome and Predictors of Clinical Renal Involvement in Patients with Silent Lupus Nephritis

Objectives: We investigated the development of clinically overt nephritis in patients with silent lupus nephritis in an effort to determine predictors of onset. Methods: We selected 31 patients with systemic lupus erythematosus (SLE) who were diagnosed as having silent lupus nephritis between 1985 and 1995. Urinalysis, blood cell count, serum creatinine, complement levels, and anti-double-stranded DNA antibody (anti-dsDNA antibody) levels were followed retrospectively for at least 60 months in each patient. Results: During the follow-up period, 8 patients developed clinical renal disease and 23 had no renal impairment. The mean time of overt nephritis onset was 58 months and renal function deteriorated mildly in 3 patients. Although clinical and laboratory findings were not significantly different at SLE onset, patients with overt nephritis showed both persistent elevation of anti-dsDNA antibodies and persistently low levels of serum C3 and CH₅₀ for at least 24 months before the onset of overt nephritis. Conclusions: Although the renal prognosis was relatively favorable, 25.8% of patients developed overt nephritis during the follow-up period. Elevation of anti-dsDNA antibodies with hypocomplementemia was persisted in these patients, suggesting the utility of these factors as predictors of clinical renal involvement in silent lupus nephritis.

Silent nephritis in systemic lupus erythematosus.

Silent lupus nephritis (SLN) was investigated in 42 renal asymptomatic patients and compared with 49 untreated patients with overt lupus nephropathy (OLN). Urinary sediment, quantitative proteinuria, creatinine clearance, antinuclear antibodies (ANA), complement, circulating immune complexes (CIC) and renal biopsies were evaluated in all of the patients. Forty-one out of the 42 (97.6%) patients had SLN according to histopathological findings. Results showed that the mean age, female/male ratio and the clinical activity index (SLEDAI) were similar in both groups (P > 0.05). The prevalence of ANA, anti-ds DNA, anti-ENA autoantibodies and C4 serum levels showed no statistical differences between the two groups (P > 0.05). Conversely, in the OLN group, elevated CIC and diminished CH50 and C3 serum levels were significantly different (P < 0.01). WHO class II was the predominant renal lesion in the group with SLN (P < 0.0001), whereas class IV was in the OLN patients (P < 0.0001). We conclude that, in our series, SLN was highly prevalent in renal asymptomatic patients with otherwise systemic lupus erythematosus. Furthermore, abnormal levels of CIC, CH50 and C3 associated with WHO class II suggest a moderate but ongoing activation of immune-mediated renal injury mechanisms.

Outcome of silent lupus nephritis

To analyze the long-term outcome in patients with silent lupus nephritis, weretrospectively studied 20 patients with systemic lupus erythematosus without clinical renal involvement who had renal biopsies in our unit between 1978 and 1986 and reviewed 193 cases reported between 1957 and 1995. Two patients of the current series were lost to follow-up. Mean follow-up in the other 18 was 13 ± 3 years (range, 2 to 17). On kidney biopsy, nine had class I, six class II, one class IV, and two class V disease (WHO classification). Three patients with prior normal renal function died of nonrenal causes. During the study, the remaining 15 patients had normal renal function and urinalysis. Most patients from the literature had “mild” histologic lesions, but 30 had diffuse proliferative glomerulonephritis. Over an average of 46 months of follow-up from biopsy, renal survival rate and patient survival rate were 98% and 91%, respectively. Three patients died of end-stage renal failure. In conclusion, end-stage renal failure in patients with silent lupus nephritis is rare regardless of the histopathological renal lesions. Patients survival depends on nonrenal causes.

Silent lupus nephritis among patients with discoid lupus erythematosus

A kidney biopsy was performed in 7 hypocomplementemic discoid lupus erythematosus patients despite the absence of overt renal involvement. Five patients had glomerular immune deposits and 2 patients with disseminated discoid lupus erythematosus exhibited definite proliferative glomerulonephritis. Those findings show that silent lupus nephritis may be encountered in discoid as well as in systemic lupus erythematosus, providing additional evidence supporting the unity of the disease. We suggest that hypocomplementemic patients with discoid lupus erythematosus must be carefully screened for renal disease by periodic urinalysis examinations.

Natural history of "silent" lupus nephritis.

Twenty patients with systemic lupus erythematosus but without evident renal involvement previously underwent percutaneous renal biopsy. Findings revealed almost universal pathologic evidence of nephritis. Included were three patients who had diffuse proliferative changes and five who had subendothelial electron dense deposits. Only four patients developed clinical renal disease during the follow-up period while no patient died or required dialysis. Using the Life Table Method, the cumulative percentage of patients free from any clinical renal disease was over 60% at 10 yr from the time of diagnosis of systemic lupus, and at 8 yr from the time of the original biopsy. It is concluded that silent lupus nephritis, regardless of histologic subtype, has a favorable prognosis. These data may not be applicable to patients with similar biopsies who have evidence of clinical lupus nephritis.