Lupus nephritis (LN), one of the most severe complications of systemic lupus erythematosus (SLE), has a complex pathogenesis involving various endogenous factors including autoimmune complex deposition, inflammatory cell infiltration, and cellular damage. Recent research has increasingly highlighted the prominent role of inflammasomes, particularly the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome, in LN pathogenesis. Substantial evidence has confirmed its significant role in both the onset and progression of LN. Given that the NLRP3 inflammasome is a critical factor in triggering and exacerbating LN, its mechanism of action warrants in-depth exploration. Furthermore, research on intervention strategies targeting the NLRP3 inflammasome to ameliorate LN is of great significance. This article reviews the latest advances in the role of the NLRP3 inflammasome in LN pathogenesis and related intervention studies, which may offer new insights for the clinical diagnosis and treatment of LN.
Humans ; Lupus Nephritis/etiology* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Inflammasomes/immunology* ; Animals

This case report concerns a 22-year-old woman who had been diagnosed with systemic lupus erythematosus (SLE). She had intermittent fever, butterfly erythema, photosensitivity, oral ulcers, and multiple arthralgia in the past seven years, but she did not adhere to regular treatments. The edema of the lower extremities and face aggravated in the recent two weeks, so she was admitted to our Department of Rheumatology and Clinical Immunology. Meanwhile, we found she had severe hypertension, the maximal blood pressure was 170/120 mmHg. The patient had high SLE disease activity (the disease activity index score was as high as 23) with blood involvement, acute renal insufficiency, multiple serous effusion and rash. After one week treatments of intravenous methylprednisolone 80 mg daily and other drugs, her conditions made some extent improvement. However, she suffered sudden epileptic attacks. No positive neuropathological signs were found, and the blood pressure was up to 190/130 mmHg before the onset of the seizures. Her cerebrospinal fluid (CSF) pressure was 330 mmH₂O, the CSF protein level was normal value, and the white blood cell count was 0 cell/mm³, with no signs of infection. Cranial MRI showed vasogenic edema at bilateral parietal, occipito-parietal regions, and centrum ovale. We prescribed drugs of decreasing intracranial pressure, intravenous drugs of decreasing blood pressure and midazolam for sedation, without corticosteroid impulse therapy. She recovered consciousness in the next day, without epilepsy recurrence. We eventually diagnosed it as posterior reversible encephalopathy syndrome (PRES), according to the history, laboratory results, imaging featuresand clinical outcome. PRES is a disorder of reversible subcortical vasogenic brain edema in patients with acute neurological symptoms (eg, seizures, encephalopathy, headache, and visual disturbances). PRES is mainly caused by blood pressure changes or endothelial injury, which lead to breakdown of the blood-brain barrier and subsequent brain edema. Most patients have a favourable prognosis. SLE complicated with PRES is not rare, especially in patients with disease activity, hypertension, lupus nephritis and/or renal insufficiency, and use of cytotoxic drugs, early recognition and appropriate treatment remain important. Brainstem involvement, intracranial hemorrhage, renal insufficiency and high disease activity of lupus are risk factors for poor prognosis.
Female ; Humans ; Lupus Erythematosus, Systemic/complications* ; Lupus Nephritis ; Magnetic Resonance Imaging ; Posterior Leukoencephalopathy Syndrome/etiology* ; Seizures ; Young Adult

Child ; Female ; Histiocytic Necrotizing Lymphadenitis ; complications ; Humans ; Lupus Erythematosus, Systemic ; etiology ; Lupus Nephritis ; complications

Adolescent ; Biological Products ; administration & dosage ; therapeutic use ; Child ; China ; Evidence-Based Medicine ; Glucocorticoids ; adverse effects ; therapeutic use ; Humans ; Immunosuppressive Agents ; administration & dosage ; therapeutic use ; Lupus Erythematosus, Systemic ; complications ; pathology ; therapy ; Lupus Nephritis ; etiology ; pathology ; therapy ; Osteoporosis ; etiology ; pathology ; therapy ; Practice Guidelines as Topic ; standards ; Severity of Illness Index ; Societies, Medical

OBJECTIVETo analyze the safety and efficacy of anti-CD20 monoclonal antibody in treatment of severe pediatric systemic lupus erythematosus (PSLE).

METHODThe diagnosis of PSLE was made according to the criteria for the classification of systemic lupus erythematosus revised by the American College of Rheumatology in 1997. Severe cases with PSLE was selected by the following criteria: age ≤ 16 years, number of important organs involved > 1, SLEDAI score > 10 points and poor response to conventional immunosuppressive treatment. These patients received 2 doses of 375 mg/m(2) rituximab (RTX), 2 weeks apart. Clinical, laboratory findings and drug side effects were recorded at RTX initiation, 2 weeks, 1 month, 3, 6 and 12 months after infusion.

RESULTA total of 20 patients. Male to female ratio was 1:3, were enrolled. They were 5-16 years old. The course of disease was (3.0 ± 2.5) years (range: 1 month-7 years), patients were followed up for 12 - 36 months [median: (27.0 ± 7.8) months]. Delirium and cognitive disorders were significantly improved in 10 cases of lupus encephalopathy after 1 month. Lupus nephritis in children were eased slowly, 14/15 patients with lupus nephritis were improved after 2-3 months. Four cases of lupus pneumonia were significantly improved within 1 month. Decreased blood cells counts were relieved at 1 month in 16/18 cases. Cellular immune function was assessed 2 weeks after application of anti-CD20 monoclonal antibody; we found B-cell clearance in 19 patients (95%). B lymphocyte count of 18 patients (90%) was restored within one year. SLEDAI score was reduced obviously. Dose of corticosteroid ranged from (45.0 ± 4.7) mg/m(2) before drug use to (12.0 ± 2.7) mg/m(2) 12 months later (P < 0.001). After the drug use, 5 patients had pneumonia within 6 months; 2 cases who suffered from aspergillus pneumonia and Pneumocystis carinii pneumonia respectively were severe. They accepted mechanical ventilation and anti-inflammatory support after being transferred to the intensive care unit, and their conditions improved at last. No death occurred. In 2 patients the disease recurred with B-cell recovery after 15 months and 18 months. Administration of another cycle of rituximab resulted in remission again in one case but not in the other.

CONCLUSIONAnti-CD20 monoclonal antibody is effective and safe in treatment of severe PSLE. But severe infections may occur in some cases. Focusing on prevention and early treatment can reduce the probability of adverse reactions.

Adolescent ; Antibodies, Monoclonal, Murine-Derived ; administration & dosage ; adverse effects ; therapeutic use ; B-Lymphocytes ; drug effects ; immunology ; Biomarkers ; blood ; Child ; Child, Preschool ; Cyclophosphamide ; administration & dosage ; Female ; Follow-Up Studies ; Glucocorticoids ; administration & dosage ; therapeutic use ; Humans ; Immunologic Factors ; administration & dosage ; adverse effects ; therapeutic use ; Lupus Erythematosus, Systemic ; complications ; drug therapy ; immunology ; Lupus Nephritis ; etiology ; pathology ; Male ; Pneumonia ; etiology ; pathology ; Prednisolone ; administration & dosage ; therapeutic use ; Rituximab ; Severity of Illness Index ; Treatment Outcome

During the last five decades, long-term therapy with immunosuppressive agents such as pulse cyclophosphamide in conjunction with high-dose corticosteroids has enhanced both patient survival and renal survival in patients with diffuse proliferative lupus nephritis. Nevertheless, severe side effects such as infectious complications remain the main cause of morbidity and mortality. Central nervous system aspergillosis is uncommon but life-threatening in lupus patients. In this single-patient case study, carotid aneurysm with sphenoidal sinusitis was suspected when severe epistaxis occurred during cyclophosphamide pulse therapy. With anti-fungal therapy, a graft stent was successfully deployed to the aneurysm and specimens of sphenoidal mucosa showed typical hyphae, indicating aspergillosis. Three months after stopping voriconazole treatment, two cerebral aneurysms that were revealed on MR images were successfully removed by aneurysmal clipping. The patient remained alive at one-year follow-up with lupus nephritis in remission. The rarity and high mortality of aspergillus-related fungal aneurysms have led to most cases being recognized postmortem. However, such aneurysms must be diagnosed early to prevent fatal complications by performing appropriate management such as surgical procedure or endovascular intervention.
Antifungal Agents/therapeutic use ; Female ; Humans ; Immunosuppressive Agents/adverse effects ; Intracranial Aneurysm/drug therapy/*etiology/surgery ; Lupus Nephritis/*complications/drug therapy ; Middle Aged ; Neuroaspergillosis/drug therapy/*etiology/surgery ; Pyrimidines/therapeutic use ; Stents ; Surgical Instruments ; Triazoles/therapeutic use

BACKGROUND/AIMS: Many studies have compared patients with systemic lupus erythematosus (SLE) on renal replacement therapy (RRT) with non-lupus patients. However, few data are available on the long-term outcome of patients with end-stage renal disease (ESRD) secondary to SLE who are managed by different types of RRTs. METHODS: We conducted a retrospective multicenter study on 59 patients with ESRD who underwent maintenance RRT between 1990 and 2007 for SLE. Of these patients, 28 underwent hemodialysis (HD), 14 underwent peritoneal dialysis (PD), and 17 patients received kidney transplantation (KT). We analyzed the clinical outcomes in these patients to determine the best treatment modality. RESULTS: The mean follow-up period was 5 +/- 3 years in the HD group, 5 +/- 3 years in the PD group, and 10 +/- 5 years in the KT group (p = 0.005). Disease flare-up was more common in the HD group than in the KT group (p = 0.012). Infection was more common in the PD and HD groups than in the KT group (HD vs. KT, p = 0.027; PD vs. KT, p = 0.033). Cardiovascular complications were more common in the HD group than in the other groups (p = 0.049). Orthopedic complications were more common in the PD group than in the other groups (p = 0.028). Bleeding was more common in the HD group than in the other groups (p = 0.026). Patient survival was greater in the KT group than in the HD group (p = 0.029). Technique survival was lower in the PD group than in the HD group (p = 0.019). CONCLUSIONS: Among patients with ESRD secondary to SLE, KT had better patient survival and lower complication rates than HD and lower complication rates than PD. The prognosis between the HD and PD groups was similar. We conclude that if KT is not a viable treatment option, any alternative treatment should take into account the patient's general condition and preference.
Adult ; Female ; Humans ; Kidney Failure, Chronic/etiology/mortality/*therapy ; Lupus Nephritis/*complications ; Male ; Middle Aged ; *Renal Replacement Therapy ; Retrospective Studies ; Treatment Outcome

OBJECTIVEAcute kidney injury (AKI) was recently proposed for early recognition of renal function impairment and prompt interventions. Previous study revealed that AKI was highly associated with the prognosis. However, there was rare report of AKI in renal diseases, especially in children cohorts. Therefore, we performed the prospective clinical research in children with renal diseases in our hospital, aiming to study the prevalence, the clinical characteristics and the short-term prognosis of AKI.

METHODThe study was designed as a prospective, single-center observational study.

INCLUSION CRITERIA(1) the primary diagnosis was primary nephrotic syndrome (NS), Henoch-Schoenlein purpura nephritis (HSPN) or lupus nephritis (LN), (2) the duration from the onset of the renal diseases to the admission was less than 3 months. The serum creatinine and urine output of the subjects would be prospectively monitored. AKI was defined by the adult criteria and stratified by Acute Kidney Injury Network (AKIN) criteria. The patients were followed up at 6 months and 12 months after enrollment.

RESULTBetween October 2007 and April 2009, a total of 95 children were included, including 65 cases with NS, 15 HSPN and 15 LN. Mean age was (8.9 ± 3.9) years (range 2 - 16 years). Thirty-three of the 95 patients (34.7%) fulfilled the AKI criteria, 13 patients (13.7%) were diagnosed as acute renal failure (ARF). All the AKI in children with LN and HSPN presented with serum creatinine elevation. However, 65.4% of AKI in NS presented with decreasing urine output, only 19.2% accompanied with increasing creatinine, with higher stages of urine output. Regarding the etiology, only 26.9% of AKI in NS had definite cause, most of which resulted from side-effect of cyclosporine, hypovolemia or tubule-interstitial damage, independent of glomerular diseases. In contrast, the AKI in LN and HSPN were exclusively caused by glomerular diseases. The length and costs of hospitalization of AKI group were significantly higher than non-AKI [length of hospitalization (d), 28(6 to 94) vs. 21(7 to 100), Z = -1.971, P = 0.049; cost of hospitalization (yuan), 12 035.7 (1561.7 to 94 783.1) vs. 8594.3 (1390.1 to 98 876.5), Z = -1.993, P = 0.046]. There was no significant difference in the serum creatinine at 6-month and 12-month follow-up between AKI group and non-AKI [6-month, (60.4 ± 91.8) µmol/L vs. (42.8 ± 12.2) µmol/L, t = 0.937, P = 0.358; 12-month, (48.7 ± 18.1) µmol/L vs. (47.7 ± 14.2) µmol/L, t = 0.197, P = 0.845].

CONCLUSIONThe prevalence of AKI (34.7%) was higher than that of ARF (13.7%) in children with renal diseases. Most of the AKI in NS resulted from non-glomerular diseases. In contrast, most AKI in LN and HSPN were caused by underlying glomerular diseases. The length and costs of hospitalization were significantly higher in AKI group. However, there was no significant difference in serum creatinine between AKI and non-AKI group in the follow-up at 6 months and 12 months. Further investigations on criteria for the diagnosis of AKI in children with renal diseases are still needed.

Acute Kidney Injury ; etiology ; Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Lupus Nephritis ; complications ; pathology ; Male ; Nephrotic Syndrome ; complications ; pathology ; Prospective Studies ; Purpura, Schoenlein-Henoch ; complications ; pathology ; Risk Factors

The variability of cardiovascular abnormalities is one of the characteristics of systemic lupus erythematosus (SLE). Among the cardiovascular manifestations, hypertension is reported in 14% to 58.1% of patients in diverse ethnic populations, and remains a clinically important issue due to its close relationship with early mortality in patients with SLE. The development of hypertension in patients with SLE has been associated with advanced lupus-related renal disease and the medications used for the treatment of lupus. Malignant hypertension is a serious complication of hypertension; it rarely occurs in patients with SLE. However, it can occur in patients with other complicated medical conditions such as the antiphospholipid antibody syndrome (APS) or cardiac tamponade. Here, we report the case of a patient with SLE and malignant hypertension with hypertensive retinopathy that initially presented without clinical evidence of APS or hypertensive nephropathy.
Adult ; Female ; Humans ; Hypertension, Malignant/*diagnosis/*etiology ; Lupus Erythematosus, Systemic/*complications/*diagnosis ; Lupus Nephritis/complications/diagnosis ; Retinal Diseases/*diagnosis/*etiology

OBJECTIVETo investigate the clinical and pathological characteristics of lupus nephritis patients complicated with malignant hypertension.

METHODSWe retrospectively studied 19 patients with lupus nephritis complicated with malignant hypertension who underwent renal biopsy between January 2002 and December 2006.

RESULTSOf 19 patients, 3 were men and 16 were women, with a mean age of 24.4 +/- 7.7 years old. All had positive antinuclear antibodies and low serum complement was found in 13 patients. All were anemic and 12 of them were thrombocytopenic. Impaired renal function was found in 17 patients with an average serum creatinine of 184.5 +/- 88.9 micromol/L. Severe intrarenal arteriolar lesion was found in all patients. Six patients had lupus vasculopathy, 11 patients had renal thrombotic microangiopathy lesion, 2 had severe arteriosclerosis. All patients received steroids and immunosuppressive drugs, 15 received angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) with resultant well-controlled blood pressure. Thrombocytopenia and hemolytic anemia resolved remarkably. The renal function improved or recovered in 14 of 17 patients, and 3 developed end-stage renal disease on maintenance dialysis.

CONCLUSIONSSevere intrarenal vascular lesion complicated with renal nephritis parallels clinical manifestation of malignant hypertension. Renal pathology is the key of treatment strategy emphasizing on the significance of renal vascular involvement and type. On the basis of immunosuppressive drugs and steroids to control systemic lupus activity, timely initiation of ACEI/ARB could be of benefit to blood pressure control and long term renal survival.

Adolescent ; Adult ; Female ; Humans ; Hypertension, Malignant ; etiology ; Kidney ; blood supply ; pathology ; Lupus Nephritis ; complications ; metabolism ; pathology ; Male ; Retrospective Studies ; Young Adult