Myeloperoxidase-ANCA IgG induces different forms of small vessel vasculitis based on type of synergistic immune stimuli.

Anti-neutrophil cytoplasmic autoantibody (ANCA) vasculitis has diverse patterns of injury including microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Necrotizing and crescentic glomerulonephritis (NCGN) occurs in all syndromes and as renal limited vasculitis (RLV). Single-dose intravenous ANCA IgG-specific for mouse myeloperoxidase (MPO) causes RLV in mice. Although multiple mouse models have elucidated ANCA-IgG induced necrotizing and crescentic glomerulonephritis (NCGN), pathogenesis of ANCA-induced granulomatosis and vasculitis outside the kidney has not been clarified. To investigate this, we used intravenous MPO-ANCA IgG in the same strain of mice to induce different patterns of lung disease mirroring patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Repeated intravenous MPO-ANCA IgG induced GPA with NCGN, lung capillaritis, arteritis and granulomatosis. Lung leukocyte phenotypes were evaluated by immunohistochemical image analysis and by flow cytometry. ANCA lung capillaritis and microabscesses began within one day and evolved into granulomas in under seven days. Influenza plus single-dose MPO-ANCA IgG induced MPA with NCGN, lung capillaritis and arteritis, but no granulomatosis. Allergic airway disease caused by house dust mites or ovalbumin plus single-dose intravenous MPO-ANCA IgG induced EGPA with eosinophilic bronchiolitis, NCGN, capillaritis, arteritis, and granulomatosis. Thus, our study shows that the occurrence and pattern of lung lesions are determined by the same ANCA IgG accompanied by different synergistic immune factors.

Pembrolizumab induced-C3 glomerulonephritis and RBC cast nephropathy: a case report.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are increasingly being used in the treatment of several cancers. Pembrolizumab is an anti-programmed cell death-1 (anti-PD-1) monoclonal antibody that is approved for the treatment of metastatic non-small cell lung cancer (NSCLC). Pembrolizumab-associated renal toxicity is relatively rare, even in pembrolizumab-associated glomerulonephritis. In this study, we report a rare case of pembrolizumab-induced C3 glomerulonephritis (C3GN) and RBC cast nephropathy. CASE PRESENTATION: A 68-year-old man with NSCLC was receiving treatment with pembrolizumab. After 19 cycles of pembrolizumab therapy, he presented with gross hematuria, severe lower-limb edema and oliguria. Laboratory tests revealed hypoalbuminemia, increased serum creatinine and low serum C3 level. Renal biopsy revealed a typical membranoproliferative glomerulonephritis accompanied by remarkable RBC casts in tubular cavities and tubulointerstitial infiltration of CD8-positive lymphocytes. Based on C3-only immunofluorescence deposit on glomeruli, a diagnosis of C3GN was made. Pembrolizumab was considered the cause of C3GN. Pembrolizumab was discontinued immediately, and 60 mg/day of prednisone was initiated. One dose of cyclophosphamide (400 mg, IV) was also administered. Upon treatment, his symptoms improved rapidly and serum creatinine decreased a lot. However, the patient became dialysis dependent eventually. CONCLUSION: This is the first case of C3GN with RBC cast nephropathy caused by ICIs. This rare case caused by the prolonged use of pembrolizumab further strengthens the relationship between ICIs and C3GN. Thus, periodic evaluation of urine and renal function is recommended in patients receiving pembrolizumab and other ICIs.

What is the prognosis of ANCA-associated glomerulonephritis with immune deposition?

OBJECTIVES: This study aimed to analyze histological and clinical characteristics of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) showing renal involvement to investigate the associations between immune complexes (IC) and clinicopathological indicators, and explore the renal outcomes of AAV. METHODS: We retrospectively evaluated the histopathological features and clinical characteristics of 80 renal biopsies of patients with AAV with renal involvement. Renal morphology was classified into two (with and without the presence of IC and complement deposition). Endpoints included end-stage kidney disease (ESKD) and death. RESULTS: Compared with patients without IC, patients with immune deposition had lower complement C3 (0.80 ± 0.27 vs. 0.93 ± 0.20, p = 0.024), more severe hematuria [133 (46-299) vs. 33 (15-115), p = 0.001] but had milder chronic pathology, including chronic tubular atrophy (p = 0.03), chronic interstitial fibrosis (p = 0.049). Patients in the immune deposition group showed a tendency to have more severe crescent formation and less glomerulosclerosis, but the difference was not statistically significant. Endpoints such as death and ESKD were not significantly different between the two groups. CONCLUSIONS: Immune deposition may indicate lower complement C3, more severe hematuria and glomerular lesions, milder tubular atrophy, and interstitial fibrosis, but it cannot predict the renal outcome.

Kinin B1 Receptor Is Important in the Pathogenesis of Myeloperoxidase-Specific ANCA GN.

BACKGROUND: Myeloperoxidase-specific ANCA (MPO-ANCA) are implicated in the pathogenesis of vasculitis and GN. Kinins play a major role during acute inflammation by regulating vasodilatation and vascular permeability and by modulating adhesion and migration of leukocytes. Kinin system activation occurs in patients with ANCA vasculitis. Previous studies in animal models of GN and sclerosing kidney diseases have demonstrated protective effects of bradykinin receptor 1 (B1R) blockade via interference with myeloid cell trafficking. METHODS: To investigate the role of B1R in a murine model of MPO-ANCA GN, we evaluated effects of B1R genetic ablation and pharmacologic blockade. We used bone marrow chimeric mice to determine the role of B1R in bone marrow-derived cells (leukocytes) versus nonbone marrow-derived cells. We elucidated mechanisms of B1R effects using in vitro assays for MPO-ANCA-induced neutrophil activation, endothelial adherence, endothelial transmigration, and neutrophil adhesion molecule surface display. RESULTS: B1R deficiency or blockade prevented or markedly reduced ANCA-induced glomerular crescents, necrosis, and leukocyte influx in mice. B1R was not required for in vitro MPO-ANCA-induced neutrophil activation. Leukocyte B1R deficiency, but not endothelial B1R deficiency, decreased glomerular neutrophil infiltration induced by MPO-ANCA in vivo. B1R enhanced ANCA-induced neutrophil endothelial adhesion and transmigration in vitro. ANCA-activated neutrophils exhibited changes in Mac-1 and LFA-1, important regulators of neutrophil endothelial adhesion and transmigration: ANCA-activated neutrophils increased surface expression of Mac-1 and increased shedding of LFA-1, whereas B1R blockade reduced these effects. CONCLUSIONS: The leukocyte B1R plays a critical role in the pathogenesis of MPO-ANCA-induced GN in a mouse model by modulating neutrophil-endothelial interaction. B1R blockade may have potential as a therapy for ANCA GN and vasculitis.

Double Filtration Plasmapheresis in the Treatment of Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis with Severe Kidney Dysfunction.

BACKGROUND: Therapeutic plasma exchange (TPE) has been recommended by guidelines for the treatment of anti-neutrophil cytoplasmic antibodies-associated vasculitis (AAV) with severe kidney dysfunction. In recent years, some researchers have proposed that double-filtration plasmapheresis (DFPP) can also be used effectively in the treatment of these patients, but the difference between the 2 modalities of plasmapheresis is not clear. METHODS: In this retrospective cohort study of AAV patients with serum creatinine ≥500 µmol/L from March 2013 to July 2018 who received TPE or DFPP treatment, we compared TPE and DFPP in terms of the changes of clinical parameters before and after plasmapheresis, the rates of adverse events during plasmapheresis, and kidney and patient survival during follow-up. RESULTS: Forty-two AAV patients with kidney injury were included in this study. Twenty patients were treated with TPE and 22 patients were treated with DFPP. All patients were followed up for a median of 22 months. In each group, there were 10 deaths, and 6 patients developed end-stage kidney disease (ESKD). There were no significant differences between TPE and DFPP in terms of the changes of renal function or other laboratory results after treatment. During the plasmapheresis treatment, there was no significant difference in the rate of adverse events (p = 0.67). During the follow-up, there was no difference between the groups regarding the level of serum creatinine for patients with kidney recovery. The hazard ratio (HR) for TPE compared to DFPP for the outcome of ESKD was 0.92 (95% CI 0.45-1.9; p = 0.79) and the HR for death was 1.11 (95% CI 0.45-2.76; p = 0.82). CONCLUSION: There were no differences in short-term effectiveness, safety, or long-term outcomes between the 2 modalities of plasmapheresis. Our study suggests that DFPP may be a choice of plasmapheresis for AAV patients with severe kidney injury especially in countries and regions with limited blood resources.

Simultaneous occurrence of IgG4-related Tubulointerstitial nephritis and colon adenocarcinoma with hepatic metastasis: a case report and literature review.

BACKGROUND: Understanding the uncommon association of IgG4-related disease with other disorders is essential for the accurate diagnosis and effective treatment of patients. To the best of our knowledge, there have been only few reports of patients with IgG4-related kidney disease coexisting with metastasis of malignancy. Here, we report a rare case of simultaneous occurring IgG4-related tubulointerstitial nephritis and colon adenocarcinoma with hepatic metastasis. CASE PRESENTATION: A 71-year-old Chinese man presented with dysuria and was initially diagnosed as benign prostatic hyperplasia for one year. He was admitted to the hospital for surgery. After admission, the renal function tests revealed a rapid increase of serum creatinine from 291.0 µmol/L to 415 µmol/L. The hemoglobin level was 89 g/L. Fecal occult blood testing was positive. Urinalysis revealed mild proteinuria. The serum IgG4 level was 13.9 g/L. The abdominal imaging examination revealed multiple solid nodules in the liver. The gastrointestinal endoscopy combined with the biopsy revealed colon adenocarcinoma. Kidney biopsy showed massive IgG4-positive plasma cells and storiform fibrosis infiltration in the tubulointerstitial area, thus establishing the diagnosis of IgG4-related tubulointerstitial nephritis. Corticosteroid therapy was initiated, and subsequently, the renal function dramatically improved without the diminution of the liver nodules. The liver biopsy was performed and a diagnosis of metastatic colon adenocarcinoma was confirmed. CONCLUSIONS: We here reported a rare case of simultaneous occurring of IgG4-related tubulointerstitial nephritis, colon adenocarcinoma with hepatic metastasis. The case highlights the importance of screening for malignancy in patients with IgG4-related disease, and the nature of the mass in other organs of patients with coexisting IgG4-related disease and malignancy should be carefully checked.

Endothelin-receptor antagonists for diabetic nephropathy: A meta-analysis.

AIM: Endothelin-receptor antagonists may be a novel therapeutic strategy for diabetic nephropathy, but their use remains controversial. This meta-analysis seeks to evaluate the effectiveness and safety of endothelin-receptor antagonists for patients with diabetic nephropathy. METHODS: Literature reviews of the PubMed, EMBASE and CENTRAL databases were conducted to identify randomized controlled trials (RCTs) comparing endothelin-receptor antagonist treatment with placebo in patients with diabetic nephropathy. Quality assessment was performed by using the Cochrane Handbook's tools for assessing risk of bias; meta-analysis was conducted by RevMan 5.3. RESUTLS: Five RCTs (n=2034 patients) were included for analysis. Compared with placebo, endothelin-receptor antagonists showed significant benefits for lowering albuminuria (five trials, n=2034 patients; SMD 0.66 95% confidence interval (CI) 0.56 to 0.76), but there was no significant difference in the risk of death (two trials, n=1674 patients; RR 1.49 95% CI 0.81 to 2.76). In addition, risk of cardiovascular events and other serious adverse events were significantly higher in the endothelin-receptor antagonists group than the placebo group (four trials, n=1956 patients; RR 1.45 95% CI 1.07 to 1.97; five trials, n=2034 patients; RR 1.32 95% CI 1.10 to 1.58). CONCLUSION: Endothelin-receptor antagonists can reduce albuminuria in patients with diabetic nephropathy, although use resulted in more serious adverse events compared with placebo. There is a potential need for further RCTs, which has larger sample size and longer duration.

The association between anti-plasminogen antibodies and disease activity in ANCA-associated vasculitis.

OBJECTIVE: Previous studies have shown that in patients with ANCA-associated vasculitis (AAV), anti-plasminogen antibodies were associated with reduced renal function and the presence of fibrinoid necrosis and cellular crescents in renal histology. The purpose of the current study was to investigate whether anti-plasminogen antibodies are associated with the systemic disease activity of AAV. METHODS: One hundred and four Chinese patients with AAV were recruited. Anti-plasminogen antibodies were detected in sequential serum samples at initial onset and remission of the disease. Associations of anti-plasminogen antibodies with clinicopathological parameters were analysed. RESULTS: The prevalence of anti-plasminogen antibodies was significantly higher in AAV patients than in healthy controls (19/104 vs 0/50, χ(2) = 8.8, P = 0.003). The prevalence of anti-plasminogen antibodies was significantly higher in the active stage of AAV than in remission (19/104 vs 1/48, χ(2) = 7.5, P = 0.013). The level of anti-plasminogen antibodies (expressed as a percentage of the positive controls) correlated with the ESR (r = 0.207, P = 0.042), serum creatinine (r = 0.302, P = 0.002), d-dimer (r = 0.273, P = 0.009) and the percentage of glomeruli with crescents in renal specimens (r = 0.393, P = 0.004). The level of Birmingham vasculitis activity scores and the prevalence of arthralgia and gastrointestinal involvement in patients with anti-plasminogen antibodies were significantly higher than in patients without anti-plasminogen antibodies [22.5 (s.d. 5.63) vs. 19.4 (s.d. 4.66), P = 0.015; 63.2% vs. 25.8%, P = 0.002; 57.9% vs. 21.1%, P = 0.001, respectively]. CONCLUSION: Circulating anti-plasminogen antibodies were associated with systemic disease activity and renal disease activity of AAV.

Analysis of Thyroid Function in ANCA-Associated Vasculitis Patients with Renal Injury.

BACKGROUND: Previous studies indicated common thyroid dysfunction in various kidney diseases. This study aimed to investigate the thyroid function in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) with renal injury. METHODS: Briefly, 174 patients diagnosed as having AAV with renal injury and without previous thyroid disease history were included in the retrospective and prospective study. The clinical parameters were collected and compared between different groups. RESULTS: Of the patients included, 24 exhibited normal thyroid function, while 150 had thyroid dysfunction, including 55 (36.67%) with hypothyroidism. Those AAV patients with thyroid dysfunction showed different clinical parameters from those with normal thyroid function. The patients were followed up for a median of 68.6 (64.3; 72.8) months. Those with thyroid dysfunction were more prone to progressing to dialysis dependence compared to the group with normal thyroid function. Logistic regression analysis showed advanced age and decreased albumin as independent risk factors for thyroid dysfunction in patients with AAV. Survival analysis and multivariate Cox regression analysis showed that thyroid dysfunction was a risk factor for AAV patients with renal injury to progress to the endpoint of dialysis dependence. CONCLUSION: Thyroid dysfunction, predominantly hypothyroidism, was commonly complicated in AAV patients with renal injury. AAV patients with thyroid dysfunction were presented with different clinical parameters and more prone to progressing to dialysis dependence compared to those with normal thyroid function.

Application of Diffusion Kurtosis Imaging and Blood Oxygen Level-Dependent Magnetic Resonance Imaging in Kidney Injury Associated with ANCA-Associated Vasculitis.

OBJECTIVE: Functional magnetic resonance imaging (fMRI) has been applied to assess the microstructure of the kidney. However, it is not clear whether fMRI could be used in the field of kidney injury in patients with Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: This study included 20 patients with AAV. Diffusion kurtosis imaging (DKI) and blood oxygen level-dependent (BOLD) scanning of the kidneys were performed in AAV patients and healthy controls. The mean kurtosis (MK), mean diffusivity (MD), and fractional anisotropy (FA) parameters of DKI, the R2* parameter of BOLD, and clinical data were further analyzed. RESULTS: In AAV patients, the cortex exhibited lower MD but higher R2* values compared to the healthy controls. Medullary MK values were elevated in AAV patients. Renal medullary MK values showed a positive correlation with serum creatinine levels and negative correlations with hemoglobin levels and estimated glomerular filtration rate. To assess renal injury in AAV patients, AUC values for MK, MD, FA, and R2* in the cortex were 0.66, 0.67, 0.57, and 0.55, respectively, and those in the medulla were 0.81, 0.77, 0.61, and 0.53, respectively. CONCLUSIONS: Significant differences in DKI and BOLD MRI parameters were observed between AAV patients with kidney injuries and the healthy controls. The medullary MK value in DKI may be a noninvasive marker for assessing the severity of kidney injury in AAV patients.

Association of the oxidative balance score and chronic kidney disease: insights from the national health and nutrition examination survey 2009-2018.

Introduction: Oxidative stress plays a pivotal role in the pathogenesis of chronic kidney disease (CKD). The oxidative balance score (OBS) was devised to quantify the overall oxidative state, integrating pro-oxidant and antioxidant influences from both dietary intake and lifestyle practices. The aim of this study was to delve into the relationship between the OBS and CKD within the adult population of the United States. Methods: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 2009-2018, we derived the OBS from 16 dietary and four lifestyle factors. We employed weighted multivariate regression to probe the link between OBS and CKD. Additionally, we undertook subgroup analyses and applied Restricted Cubic Spline Regression (RCS) for further data analyses. Results: This study encompassed 19,444 participants. Logistic regression analysis consistently demonstrated a protective effect of higher OBS on CKD. In Model 3, each unit increase in OBS was associated with a 2% reduction in the risk of CKD (95% CI: 0.97-0.99, p < 0.001) and a 4% reduction in the risk of reduced estimated glomerular filtration rate (eGFR) (95% CI: 0.95-0.98, p < 0.001). The highest OBS quintile (Q4) also showed significant reductions in the risk of CKD (OR: 0.66, 95% CI: 0.53-0.82, p < 0.001) and reduced eGFR (OR: 0.51, 95% CI: 0.37-0.69, p < 0.001) in Model 3. RCS analysis revealed a linear relationship between OBS and CKD. Subgroup analyses indicated significant associations between OBS and CKD in most subgroups, except for those without hypertension or with cardiovascular disease. Additionally, interaction analyses demonstrated that age, hypertension, and diabetes significantly modify the association between OBS and CKD risk. Conclusion: An elevated OBS, reflecting a predominance of antioxidants, correlates with a diminished CKD risk in the American adult demographic. These insights emphasize the potential influence of oxidative equilibrium on the development of CKD.

Circulating complement activation in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis.

Studies in animal models suggest that complement activation is crucial in the pathogenesis of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). Here we investigate the circulating complement activation profile of 66 patients with active stage AAV compared to that of 54 patients with AAV in remission. Plasma levels of C3a, C5a, soluble C5b-9, and Bb, all determined by enzyme-linked immunosorbent assay, were significantly higher in active stage than in remission of AAV, while plasma levels of properdin were significantly lower in the former than the latter disease stage. There was no significant difference in the plasma levels of C4d between active stage and remission. The plasma level of Bb in patients with active AAV significantly correlated with the proportion of total and cellular crescents in the renal biopsy, the erythrocyte sedimentation rate, and the Birmingham Vasculitis Activity Scores. Thus, systemic activation of complement by the alternative pathway takes place in human AAV. Circulating Bb might be a useful biomarker in assessing disease activity of AAV.

Influence of variable domain glycosylation on anti-neutrophil cytoplasmic autoantibodies and anti-glomerular basement membrane autoantibodies.

BACKGROUND: The pathophysiological significance of variable region glycosylation of autoantibodies is still unclear. In the current study, the influence of the variable region N-linked oligosaccharides on the reactivity of three autoantibody specificities was investigated with Sambucus nigra agglutinin (SNA), which mainly binds to oligosaccharides with terminal α2, 6-linked sialic acid on the variable region of IgG. METHODS: Twenty-seven patients with serum positive anti-neutrophil cytoplasmic autoantibodies (ANCA) against myeploperoxidase (MPO) or proteinase 3 (PR3), or autoantibodies against glomerular basement membrane (GBM) were included. Total IgG was isolated and separated into non-SNA-binding and SNA-binding fractions with SNA affinity chromatography. Antigen-specific IgG was purified by immunoaffinity chromatography. RESULTS: At the same concentration of IgG, the antigen binding level of non-SNA-binding IgG was significantly lower than that of SNA-binding IgG for MPO-ANCA (absorbance value at 405 nm, 0.572 ± 0.590 vs. 0.962 ± 0.670, P < 0.001) and for PR3-ANCA (0.362 ± 0.530 vs. 0.560 ± 0.531, P = 0.003). The antigen binding level of non-SNA-binding IgG was significantly higher than that of SNA-binding IgG for anti-GBM antibodies (1.301 ± 0.594 vs. 1.172 ± 0.583, P = 0.044). The level of variable region glycosylation of total IgG was significantly lower than that of affinity-purified MPO-ANCA (1.021 ± 0.201 vs. 1.434 ± 0.134, P = 0.004). The level of variable region glycosylation of total IgG was significantly higher than that of affinity-purified anti-GBM antibodies (1.034 ± 0.340 vs. 0.734 ± 0.333, P = 0.007). The SNA-binding fraction of MPO-ANCA-containing IgG and PR3-ANCA-containing IgG induced higher levels of neutrophil oxygen radical production than the corresponding non-SNA-binding fractions (P < 0.001 and P = 0.043, respectively). The level of variable region glycosylation of affinity-purified MPO-ANCA was higher in active AAV than the same patients in remission (P = 0.001). CONCLUSION: Characteristics of variable region glycosylation of ANCA and anti-GBM antibodies were different from that of total IgG, which might influence the antigen-binding ability of these antibodies. Variable region glycosylation of ANCA might influence the effect of ANCA-induced neutrophils respiratory burst.

The Sustained and Marked Elevation of Serum Procalcitonin in a Hemodialysis Patient with Tuberculous Lymphadenitis, but Without the Evidence of Sepsis: A Case Report.

Background: The elevation of serum procalcitonin (PCT) has been considered as a marker of systemic bacterial infection and sepsis. However, the marked elevation of PCT in non-sepsis conditions was rare. Here, we report a rare case of sustained markedly elevation of serum PCT in a dialysis patient with tuberculosis, but without the evidence of sepsis. Case Presentation: A 25-year-old man on maintenance hemodialysis was admitted to the hospital for kidney transplantation. On admission, physical examination revealed multiple lymph nodes were palpable on both sides of the neck which was later confirmed as tuberculosis with biopsy pathology. On the 3rd day after admission, the patient suffered from fever with a temperature of 38.8°C. The white blood cells 12.35 × 109/L and the PCT level was 5.73 ng/mL. Lately the PCT increased to 63.10 ng/mL, and the level of C-reactive protein was 186.00 mg/L. After the antibiotics upgraded from cefmetazole to meropenem, and vancomycin was added, the body temperature dropped to the normal range on the 17th day and remained normal thereafter. The PCT level declined gradually to 4.18 ng/mL on the 21st day and an antituberculosis regimen was started. After that, the PCT levels fluctuated between 2.9 ng/mL and 94.9 ng/mL without any manifestation of sepsis. The markedly elevation of serum PCT level persisted despite normal C-reactive protein level and leukocyte counts. Conclusion: Persistently elevated serum PCT level might occur in conditions without evidence of sepsis. Taking consideration of multiple inflammatory factors to determine infection when the markedly elevated PCT level was not correlated with the clinical manifestations.

Anti-glomerular basement membrane disease with rupture of the newly formed bilateral corpus luteum cysts: A case report.

RATIONALE: Anti-glomerular basement membrane (anti-GBM) disease during gestation is sparse and even rarer when combined with bilateral large corpus luteum cysts. In this case, we report a case of anti-GBM disease in the early stage of pregnancy with ruptured newly formed bilateral large corpus luteum cysts. PATIENT CONCERNS: A 24-year-old female was initially diagnosed with anti-GBM disease. During treatment, abdominal distention and vaginal bleeding successively staged. The results of the first gynecological ultrasound and abdominal CT were negative. DIAGNOSIS: Based on the dynamic imaging change of the ovaries, the elevated human chorionic gonadotropin (hCG) and sex hormones, and the pathological findings, a diagnosis of anti-GBM disease with rupture of the newly formed bilateral corpus luteum cysts during early pregnancy was considered. INTERVENTIONS: The patient was treated with corticosteroids, plasma-exchange along with intensive hemodialysis. Then, to confirm the diagnosis, laparoscopic debulking of bilateral ovarian cysts and curettage were performed. OUTCOMES: After treatment, the anti-GBM antibody titer declined and the condition of the patient was still stable 2 months following discharge. LESSONS: As clinicians, we should be aware that even if the first imaging tests are negative, the relevant indicators should be reviewed dynamically based on the condition of the patients. Additionally, this case raised the question of whether anti-GBM disease was associated with pregnancy and giant corpus luteum cysts, which needs further investigations.

Understanding the Gut-Kidney Axis in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: An Analysis of Gut Microbiota Composition.

Increasing evidence suggested that gut microbiota played critical roles in developing autoimmune diseases. This study investigated the correlation between gut microbiota and antineutrophil cytoplasmic antibody-associated vasculitis (AAV) with kidney injury. We analyzed the fecal samples of 23 AAV patients with kidney injury using a 16s RNA microbial profiling approach. The alpha-diversity indexes were significantly lower in AAV patients with kidney injury than healthy controls (Sobs P < 0.001, Shannon P < 0.001, Chao P < 0.001). The beta-diversity difference demonstrated a significant difference among AAV patients with kidney injury, patients with lupus nephritis (LN), and health controls (ANOSIM, p = 0.001). Among these AAV patients, the Deltaproteobacteria, unclassified_o_Bacteroidales, Prevotellaceae, Desulfovibrionaceae Paraprevotella, and Lachnospiraceae_NK4A136_group were correlated negatively with serum creatinine, and the proportion of Deltaproteobacteria, unclassified_o_Bacteroidales, Desulfovibrionaceae, Paraprevotella, and Lachnospiraceae_NK4A136_group had a positive correlation with eGFR. In conclusion, the richness and diversity of gut microbiota were reduced in AAV patients with kidney injury, and the alteration of gut microbiota might be related with the severity of kidney injury of AAV patients. Targeted regulation of gut microbiota disorder might be a potential treatment for AAV patients with kidney injury.

Toll-like Receptors as Potential Therapeutic Targets in Kidney Diseases.

Toll-like Receptors (TLRs) are members of pattern recognition receptors and serve a pivotal role in host immunity. TLRs response to pathogen-associated molecular patterns encoded by pathogens or damage-associated molecular patterns released by dying cells, initiating an inflammatory cascade, where both beneficial and detrimental effects can be exerted. Accumulated evidence has revealed that TLRs are closely associated with various kidney diseases but their roles are still not well understood. This review updated evidence on the roles of TLRs in the pathogenesis of kidney diseases including urinary tract infection, glomerulonephritis, acute kidney injury, transplant allograft dysfunction and chronic kidney diseases.