Introduction: Among various lupus renal vascular changes, thrombotic microangiopathy (TMA) presented with the most severe clinical manifestations and high mortality. The pathogenesis of TMA in systemic lupus erythematosus (SLE) was complicated. The aim of this study was to assess clinical manifestations, laboratory characteristics, pathological features and risk factors for clinical outcomes of lupus nephritis patients co-existing with renal TMA in a large cohort in China. Methods: Clinical and renal histopathological data of 148 patients with biopsy-proven lupus nephritis were retrospectively analyzed. Serum complement factor H, A Disintegrin and Metalloprotease with Thrombospondin type I repeats 13 (ADAMTS-13) activity, antiphospholipid antibodies and C4d deposition on renal vessels were further detected and analyzed. Results: In the 148 patients with lupus nephritis, 36 patients were diagnosed as co-existing with renal TMA based on pathological diagnosis. Among the 36 TMA patients, their clinical diagnoses of renal TMA were as followings: 2 patients combining with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome, 2 patients combining with anti-phospholipid syndrome, 2 patients with malignant hypertension, 1 patient with scleroderma and the other 29 patients presenting with isolated renal TMA. Compared with the non-renal TMA group, patients with renal TMA had significantly higher urine protein (7.09 ± 4.64 vs. 4.75 ± 3.13 g/24h, P = 0.007) and serum creatinine (159, 86 to 215 vs. 81, 68 to 112 μmol/l, P <0.001), higher scores of total activity indices (AI) (P <0.001), endocapillary hypercellularity (P <0.001), subendothelial hyaline deposits (P = 0.003), interstitial inflammation (P = 0.005), glomerular leukocyte infiltration (P = 0.006), total chronicity indices (CI) (P = 0.033), tubular atrophy (P = 0.004) and interstitial fibrosis (P = 0.018). Patients with renal TMA presented with poorer renal outcome (P = 0.005) compared with the non-TMA group. Renal TMA (hazard ratio (HR): 2.772, 95% confidence interval: 1.009 to 7.617, P = 0.048) was an independent risk factor for renal outcome in patients with lupus nephritis. The renal outcome was poorer for those with both C4d deposition and decreased serum complement factor H in the TMA group (P = 0.007). Conclusions: There were various causes of renal TMA in lupus nephritis. Complement over-activation via both classical and alternative pathways might play an important role in the pathogenesis of renal TMA in lupus nephritis.

Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1 (rs230540, OR = 1.25, P = 3.4 × 10⁻¹²) and IRF4 (rs9405192, OR = 1.29, P = 1.4 × 10⁻¹⁴), fine-map the PLA2R1 locus (rs17831251, OR = 2.25, P = 4.7 × 10⁻¹⁰³) and report ancestry-specific effects of three classical HLA alleles: DRB1*1501 in East Asians (OR = 3.81, P = 2.0 × 10⁻⁴⁹), DQA1*0501 in Europeans (OR = 2.88, P = 5.7 × 10⁻⁹³), and DRB1*0301 in both ethnicities (OR = 3.50, P = 9.2 × 10⁻²³ and OR = 3.39, P = 5.2 × 10⁻⁸², respectively). GWAS loci explain 32% of disease risk in East Asians and 25% in Europeans, and correctly re-classify 20–37% of the cases in validation cohorts that are antibody-negative by the serum anti-PLA2R ELISA diagnostic test. Our findings highlight an unusual genetic architecture of MN, with four loci and their interactions accounting for nearly one-third of the disease risk.

SUMMARY: A recent development in the field of vasculitis is the increasing recognition that certain medications such as propylthiouracil can induce anti‐neutrophil cytoplasmic antibodies (ANCA)‐associated vasculitis (AAV). This review focuses on the data on causal drugs, possible pathogenesis, clinical description, diagnosis, treatment and prognosis of patients with drug‐induced AAV. The pathogenesis of drug‐induced AAV might be multifactorial. The clinical manifestations are similar to those of primary AAV, but ANCA with multi‐antigenicity may help to differentiate it from primary AAV. The diagnosis of drug‐induced AAV is based on the temporal relationship between clinically evident vasculitis and administration of the offending drugs, and excluding medical conditions that mimic vasculitis and other definable types of vasculitis. After the diagnosis of drug‐induced AAV was made, the offending drugs should be withdrawn immediately, and appropriate immunosuppressive therapy should be administered only for patients with vital organ involvement. The duration of immunosuppressive therapy should be much shorter than that in primary AAV and long‐term maintenance therapy might not be necessary. The prognosis of patients with drug‐induced AAV is good as long as the offending drug is discontinued in time.

Background: Fine particulate matter (PM_2.5) is an important environmental risk factor for cardiopulmonary diseases. However, the association between PM_2.5 and risk of CKD remains under-recognized, especially in regions with high levels of PM_2.5, such as China. Methods: To explore the association between long-term exposure to ambient PM_2.5 and CKD prevalence in China, we used data from the China National Survey of CKD, which included a representative sample of 47,204 adults. We estimated annual exposure to PM_2.5 before the survey date at each participant’s address, using a validated, satellite-based, spatiotemporal model with a 10 km×10 km resolution. Participants with eGFR <60 ml/min per 1.73 m² or albuminuria were defined as having CKD. We used a logistic regression model to estimate the association and analyzed the influence of potential modifiers. Results: The 2-year mean PM_2.5 concentration was 57.4 μg/m³, with a range from 31.3 to 87.5 μg/m³. An increase of 10 μg/m³ in PM_2.5 was positively associated with CKD prevalence (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.22 to 1.35) and albuminuria (OR, 1.39; 95% CI, 1.32 to 1.47). Effect modification indicated these associations were significantly stronger in urban areas compared with rural areas, in males compared with females, in participants aged <65 years compared with participants aged ≥65 years, and in participants without comorbid diseases compared with those with comorbidities. Conclusions: These findings regarding the relationship between long-term exposure to high ambient PM_2.5 levels and CKD in the general Chinese population provide important evidence for policy makers and public health practices to reduce the CKD risk posed by this pollutant.