Membranous nephropathy associated with IgG4-related disease successfully treated with obinutuzumab

IgG4-releated disease is typically associated with interstitial nephritis, but rare cases of idiopathic membranous nephropathy as renal manifestation have been described. Obinutuzumab was successfully used in refractory membranous nephropathy, but evidence for the treatment of IgG4-related disease with obinutuzumab is lacking so far. We report one patient's case with membranous nephropathy associated with IgG4-related disease, who was treated with obinutuzumab following anaphylactic reaction to rituximab. Obinutuzumab treatment resulted in a sustained complete remission of membranous nephropathy and decrease of IgG4 to the normal range. This case demonstrates that membranous nephropathy associated with IgG4-related disease can successfully be treated with obinutuzumab.

Use of biologic agents and methotrexate improves renal manifestation and outcome in patients with rheumatoid arthritis: a retrospective analysis

Background and purpose We examined whether advances in treatment strategies from older disease-modifying antirheumatic drugs (DMARDs) to new biologic agents and methotrexate improved renal complications and outcome in patients with rheumatoid arthritis (RA). Methods We reviewed records of 156 patients with RA who underwent kidney biopsy at our institute between January 1990 and December 2019. All patients were assigned to one of three periods: period 1, 1990–1999 (n = 48); period 2, 2000–2009(n = 57); period 3, 2010–2019 (n = 51). Results Membranous nephropathy, nephrosclerosis, AA-amyloidosis, and IgA nephropathy were the four major renal manifestations of RA. AA-amyloidosis was diagnosed by kidney biopsy in 21 patients: period 1, 7 patients (15%); period 2, 10 patients (18%); and period 3, 4 patients (8%). The 4 patients in period 3 were in the years 2010–2014, and no new case of AA-amyloidosis was recorded from 2015 to 2019. In all 21 of the patients with AA-amyloidosis, neither a biologic agent nor methotrexate was administered. Fifteen of the 21 patients required dialysis, and 13 died in periods 1–3 because of amyloid-related cardiac dysfunction less than 2 years after the initiation of dialysis. Two of them are doing well using biologic agent despite dialysis. The remaining three patients who received a biologic agent or methotrexate does not progress to end-stage renal failure. In addition, the other renal complications showing progression to dialysis also decreased over time. Conclusion Advances in treatment strategies have improved renal outcome and reduced mortality in patients with RA.

P017 Complications of Juvenile Idiopathic Arthritis

Background Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disease characterized by onset before the age of 16. This term encompasses several disease categories, each of which has distinct methods of presentation, clinical signs, and prognosis. The study aimed to determine JIA complications in 51 patients. Methods A cross-sectional study including patients diagnosed with JIA according to ILAR criteria was conducted for 26 years [1995– 2021]. Epidemiological, clinical, therapeutic, and evolutive aspects were noted. Results Twenty-nine males and 22 females were included. The mean age of the disease onset was 7.6 years [1,5–16]. The mean age of patients at the time of the study was 23.29 years [9–45]. Polyarticular and seronegative form was the most frequent (34.5%). Other subtypes diagnosed were systemic (25%), enthesitis-related arthritis (21.2%), oligoarticular (12.5%), and seropositive polyarticular (5.8%). Standard X-Ray imaging showed articular damage in 50% of the cases. Hip arthritis was observed in 32% and surgery was needed in 16.9%. One patient presented with atlantoaxial subluxation. Growth retardation was noted in 28.6%. Cardiac manifestations were seen in 3 patients (pericarditis = 2, myocarditis = 1), uveitis in 3 cases, renal manifestation (extra membranous glomerulonephritis) in one patient with polyarticular form. One patient was diagnosed with multiple sclerosis. Small doses of corticosteroids were prescribed in 71.7%. Methotrexate was prescribed in 70.5% (interrupted for adverse effects in 3 patients), sulfasalazine in 30.6%, hydroxychloroquine in 5.7%, leflunomide in 15.4%. bDMARDs were needed in 16 patients: 14 patients received TNF alpha inhibitors, rituximab was prescribed for one patient with a polyarticular form, and tocilizumab in a patient with a systemic form. A switch of bDMARDs was conducted in 10 patients: for inefficiency in 4 cases and adverse effects in other 4 cases. Three patients developed uveitis under Etanercept, septicemia under Adalimumab, an allergic reaction, and depression under Infliximab. One patient died from a convulsive seizure at the age of 9. Conclusion The presence of complications is an additional burden to JIA patients. A multidisciplinary approach is required for the management of these complications.

Predictive Ability of Serum IL-27 Level for Assessing Activity of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

Serum interleukin- (IL-) 27 level has been reported to increase in patients with several autoimmune diseases; however, its significance in patients with antineutrophil cytoplasmic antibody- (ANCA-) associated vasculitis (AAV) is unknown. In this study, we investigated the associations between serum IL-27, laboratory features, and activity of AAV and evaluate the predictive ability of serum IL-27 level for disease activity. This study included 77 AAV patients, and we collected clinical and laboratory data at blood sampling. Inflammation-related variables included white blood cell, neutrophil, lymphocyte and platelet counts, serum albumin, erythrocyte sedimentation rate, and C-reactive protein levels. Serum IL-27 and IL-18 levels were measured from stored sera using Human Magnetic Luminex® assay. High disease activity of AAV was defined as the highest tertile of Birmingham vasculitis activity score (BVAS) (≥11). The mean age of the enrolled patients was 59.9 years, and 38 (49.4%) were diagnosed as microscopic polyangiitis. In the multivariable analysis, serum albumin ( β = − 0.419 ) and serum IL-27 level ( β = 0.221 ) were significantly associated with BVAS. Furthermore, patients with renal manifestation exhibited higher serum IL-27 (mean 308.7 pg/mL vs. 105.8 pg/mL) and IL-18 levels (mean 376.7 pg/mL vs. 270.4 pg/mL) than those without. On applying the optimal cut-off of serum IL-27 level for predicting high activity, AAV patients with serum IL − 27 level ≥ 300.8 pg/mL had a significantly higher risk for having high disease activity than those with serum IL − 27 level < 300.8 pg/mL (relative risk 3.380, 95% confidence interval 1.223, 9.345, P = 0.016 ). These results suggest that serum IL-27 level is associated with the cross-sectional activity and the presence of renal manifestation and could be used to predict high disease activity in patients with AAV.

Chemokine/Cytokine Levels Correlate with Organ Involvement in PR3-ANCA-Associated Vasculitis

Background: ANCA-associated vasculitis (AAV) is a rare small vessel disease characterized by multi-organ involvement. Biomarkers that can measure specific organ involvement are missing. Here, we ask whether certain circulating cytokines and chemokines correlate with renal involvement and if distinct cytokine/chemokine patterns can differentiate between renal, ear/nose/throat, joints, and lung involvement of AAV. Methods: Thirty-two sets of Birmingham vasculitis activity score (BVAS), PR3-ANCA titers, laboratory marker, and different cytokines were obtained from 17 different patients with AAV. BVAS, PR3-ANCA titers, laboratory marker, and cytokine concentrations were correlated to different organ involvements in active AAV. Results: Among patients with active PR3-AAV (BVAS > 0) and kidney involvement we found significant higher concentrations of chemokine ligand (CCL)-1, interleukin (IL)-6, IL21, IL23, IL-28A, IL33, monocyte chemoattractant protein 2 (MCP2), stem cell factor (SCF), thymic stromal lymphopoietin (TSLP), and thrombopoietin (TPO) compared to patients without PR3-ANCA-associated glomerulonephritis. Patients with ear, nose, and throat involvement expressed higher concentrations of MCP2 and of the (C-X-C motif) ligand-12 (CXCL-12) compared to patients with active AAV and no involvement of these organs. Conclusion: We identified distinct cytokine patterns for renal manifestation and for ear, nose and throat involvement of PR3-AAV. Distinct plasma cytokines might be used as non-invasive biomarkers of organ involvement in AAV.

Tubular cell damage may be the earliest sign of renal extrahepatic manifestation caused by Hepatitis C

Chronic kidney disease (CKD) is one of the most well-known extrahepatic manifestations caused by hepatitis C infection (HCV). CKD is typically discovered at a late stage. HCV-nephropathy may show different histopathologic patterns, as both glomerular and tubulointerstitial damage have been described. Identification of patients with early renal manifestations would be beneficial to provide treatment and avoid progression to CKD. The observational prospective single-center HCVKID study assessed the prevalence of early renal manifestations in patients with chronic HCV and compared these patients with HCV-negative healthy controls cross-sectionally. HCV-positive patients with and without renal manifestations were also compared to define biomarkers suitable for identifying early manifestations in standard clinical practice. Tubular proteinuria as judged by urine α 1-microglobulin was the most common early renal manifestation found in 11% in HCV-positive patients, followed by hematuria in 8%. Kidney filtration was statistically significantly lower among HCV-positive patients with renal manifestation according to any calculation method. There were no significant differences in duration of infection or stage of liver fibrosis between patients with or without renal manifestations. Tubular cell damage may be the earliest sign of renal dysfunction caused by HCV. Complement activation also correlates with the dysfunction, indicating of contribution to HCV-induced renal manifestations even in their early phase.

The New Compound Heterozygous Mutation of NUP Nephropathy: Report of Two Cases and Literature Review

Backgrounds: NUP nephropathy is identified as a rare monogenic cause of steroid-resistant nephrotic syndrome recently. To explore the relationship between NUP mutation and renal disorders, we provide two cases and a literature review of the genotypical and phenotypical features in patients with NUP nephropathy.Results: We reported two patients with newly diagnosed NUP nephropathy who carried a compound heterozygous mutations in NUP107 and NUP93 gene respectively. Both patients were diagnosed steroid-resistant nephrotic syndrome and progressed to end-stage renal disease in childhood. While the mutation c.1537+1G>A in NUP93 gene was previously described, the mutations c.460A>G and c.1085C>T in NUP107 gene and c.1472A>T in NUP93 gene were novel. We also summarized the phenotypic and genetic spectrum of NUP nephropathy in eighty-six reported patients who carried 50 different mutations in 6 NUP genes (NUP107, NUP93, NUP205, NUP85, NUP133, NUP160). The majority of them were Asians (66/86, 76.7%). The mutation c.2492A>C and c.1079-1083del in NUP107 had been identified as the founder mutations in East Asian[1-3], while c.1772G>T and c.1886A>G in NUP93 might be the founder mutations in Western Europe and Turkish respectively. Nephrotic syndrome was the most common renal manifestation (68/86, 79.1%). Although the renal prognosis was poor that 80.8% (59/73) of them developed end-stage renal disease within the first two decades, the outcome of renal transplantation in NUP nephropathy is better than patients with other steroid-resistant nephrotic syndrome. Focal segmental glomerulosclerosis was the most prevalent renal biopsy pathologic type (56/65, 86.1%). Various extra-renal manifestations were found in 44.8% (26/58) of patients. Neurological involvement was the most common extra-renal presentation (22/26, 84.6%), including microcephaly (13/22, 59.1%), intellectual disability (12/22, 54.5%), and global developmental delay (10/22, 45.5%). Diverse abnormalities of the facial appearance (8/26, 30.8%), short stature (5/26, 19.2%),and contain convergent strabismus (4/26, 15.4%) had also been reported. There are significant differences in extra-renal manifestations between different genomics. Conclusions: The renal manifestation of NUP nephropathy is highly consistent that most patients suffered early-onset SRNS with FSGS. More than half of the patients had extra-renal symptom concomitantly. Asians showed potential susceptibility to NUP nephropathy. Despite the limited reports, some genotype-phenotype correlations have been gradually revealed.