Patients with IgA vasculitis (IgAV), an immune complex-mediated disease, may exhibit kidney involvement—IgAV with nephritis (IgAVN). The kidney-biopsy histopathologic features of IgAVN are similar to those of IgA nephropathy, but little is known about histopathologic disease severity based on the interval between purpura onset and diagnostic kidney biopsy. We assessed kidney histopathology and clinical and laboratory data in a cohort of adult patients with IgAVN (n = 110). The cases were grouped based on the interval between the onset of purpura and kidney biopsy: Group 1 (G1, 6 months, n = 38). Glomerular leukocytes were more common in G1 than in the other groups (p = 0.0008). The proportion of neutrophils among peripheral-blood leukocytes was the highest in the patients biopsied within a month after onset of purpura (G1: 71 ± 8%). In the patients with an interval >6 months, the neutrophil proportion was lower, 60%. Moreover, the glomerular mesangial proliferation score correlated with the serum total IgA concentration (p = 0.0056). In conclusion, IgAVN patients biopsied <1 month from purpura onset showed an elevated percentage of blood neutrophils and glomerular leukocytes, consistent with an acute-onset inflammatory reaction. In all IgAVN patients, the mesangial proliferation score correlated with the serum IgA level.

Objective: Adult immunoglobulin A vasculitis (IgAV) is documented to be associated with more renal involvement and poorer renal outcomes compared to children, but adult IgAV nephritis (IgAV-N) data are rather limited. The present study aimed to describe the characteristics of adult IgAV-N and investigate the long-term prognostic factors.Methods: Clinical and morphological data from 106 adult patients with biopsy-proven IgAV-N and follow-up data from 94 patients in a single Chinese center were analyzed in this retrospective study. Median follow-up time interval was 102 months.Results: The median age of patients with IgAV-N at biopsy was 38 (IQR 24-53) years, and 52.8% were male. The median blood pressure was 126/80 mmHg, and 25.5% of patients were hypertensive at baseline. The median initial proteinuria was 1.4 (IQR 0.7-2.2) g/day and estimated glomerular filtration rate (eGFR) was 103 (IQR 84-121) mL/min/1.73 m². The median time interval of onset to biopsy was 8 (IQR 3-40) weeks. In biopsy, the median percentage of global sclerosis was 5.9% (IQR 0.0-13.8), whereas 45.3% of patients had interstitial fibrosis and tubular atrophy. Further, during follow-up, 7.4% patients died, 4.3% patients progressed to endstage kidney disease (ESKD), and 6.4% patients developed > 30% eGFR reduction from baseline. Multivariate Cox proportional analyses revealed hypertension (HTN) history and > 10% global sclerosis at presentation were independent prognostic factors for poor outcome.Conclusion: The present adult IgAV-N cohort revealed a relatively young onset age, and lower incidence of nephrotic syndrome and ESKD. Moreover, nonimmune factors such as history of HTN and renal chronic histological lesions in biopsy played a crucial role in prognosis of IgAV-N.

We aimed to explore the associated factors of endothelial injury in chronic kidney disease (CKD) and the relationship between endothelial dysfunction and CKD prognosis. A prospective observational cohort study. 77 adults with CKD stages 1-5 were enrolled January 2010 to December 2010 and followed up until December 2015. Serum asymmetric dimethylarginine (ADMA) level at baseline, α-klotho, sodium-phosphorus synergistic transporter, and dimethylarginine-dimethylamine hydrolase expression in kidney biopsy samples. Initiation of kidney replacement therapy (KRT). Kaplan-Meier analysis was used for evaluation of the incidence rate of KRT. All tests were 2 tailed, and statistical significance was defined as P < 0.05. Mean serum ADMA level of 77 patients was 64.3 ± 34.6 ng/mL. ADMA level increased with CKD stages (P = 0.06) and declining kidney function (r = −0.267; P = 0.02). The expression of α-klotho in kidney biopsy specimens also decreased. Median follow-up time was 56 (interquartile range, 50.5-62) months. Kaplan-Meier analyses showed that during a total follow-up of 6 years, the incidence of KRT initiation in the high-ADMA group was significantly higher than that in the low group (35.9% vs 13.2%; P = 0.03). ADMA level was negatively correlated with α-klotho (r = −0.233; P = 0.04) and positively correlated with phosphorus level (r = 0.243; P = 0.04). The expression of sodium-phosphorus synergistic transporter in kidney tubules, which promoted phosphorus reabsorption, and the expression of dimethylarginine-dimethylamine hydrolase isoform 1, which regulated ADMA, were decreased. Correlation analysis also showed that ADMA level decreased while age increased at baseline (r = −0.292; P = 0.01). Small sample size with limited longer-term follow-up. Serum ADMA levels increased as kidney function declined, and high serum ADMA level was associated with incident kidney failure. Low tissue α-klotho and high levels of plasma phosphorus or tissue expression of type II sodium/phosphate cotransporter in the kidney are associated with higher circulating ADMA levels, suggesting that they may be involved in the pathogenesis of endothelial dysfunction in patients with CKD.

Introduction: It′s crucial to utilize combination therapy for IgAN patients to reduce proteinuria and maintain stable kidney function. We demonstrate the safety and efficacy of low-dose spironolactone in management of IgAN patients. Methods: Adult IgAN patients treated with spironolactone were evaluated. Patients were separated into two categories according to whether 24h-proteinuria was reduced by more than 20% after two-months of spironolactone treatment compared to baseline levels. Results: 88 patients were analyzed and 24h-proteinuria decreased from 0.93g to 0.70 g (p＜0.001) after two-months of treatment with spironolactone, accompanied by a slight decrease in EPI-eGFR from 75.7 to 73.9 mL/min/1.73 m2 (p = 0.033). Intriguingly, 47 patients in effective MRA group showed less endocapillary hypercellularity (p = 0.040). In ineffective group, 18 patients discontinued MRA treatment because of 24h-proteinuria increased from 0.83 g to 1.04 g, while the other 23 patients were continued with spironolactone and proteinuria decreased to 0.57 g in the sixth month (p = 0.001). Furthermore, 12 patients with persistent high proteinuria during prednisone therapy, were added with spironolactone. 24-proteinuria were dropped from 0.95 g to 0.73 g at the second month, and to 0.50 g at the sixth month. Conclusions: In our study, we confirmed spironolactone's efficacy in reducing urine protein excretion in IgA nephropathy patients within two months of treatment. However, response varied among patients, with those showing endocapillary proliferation (E1) in renal biopsies having poor spironolactone responsiveness. Administering mineralocorticoid receptor antagonists (MRAs) to patients with eGFR over 30 ml/min did not result in hyperkalemia, indicating the treatment's safety. Key Words：IgA Nephrology, Proteinuria, Spironolactone, Renal function

Membranous nephropathy (MN) is characterized by subepithelial immune complex deposits of IgG, particularly anti-Phospholipase A2 Receptor (anti-Pla2r). However, presence of IgA co-deposition along subepithelial region of the glomerular capillary walls has not been extensively investigated. Five hundred thirty-one biopsy-proven MN patients from Huashan Hospital were screened for capillary IgA deposition. Clinical, biological and histopathological data were collected at biopsy and during follow-ups. A propensity score matched cohort was used to compare treatment response and outcomes between MN patients with capillary co-deposition of IgG and IgA (cIgA-MN) and MN without. Immunofluorescence was used to detect IgA, IgG, Galactose deficient-IgA1 (Gd-IgA1) and Pla2r deposition. ELISA was performed to measure circulating Gd-IgA1 level. IgA and IgG subtypes of sera anti-Pla2r antibodies were investigated by indirect immunofluorescence and validated by ELISA. Fifty-three of 531 MN patients exhibited capillary IgA co-deposition with IgG. Secondary causes were identified in 19 of 53 cIgA-MN patients. The remaining 34 primary cIgA-MN patients had median proteinuria of 6.1 g/day and showed no crescents and mild endocapillary proliferation. 73.5% cIgA-MN patients were positive for Pla2r. Gd-IgA1 was absent in glomeruli of cIgA-MN patients and circulating Gd-IgA1 levels were similar to those in MN patients without IgA deposition. Meanwhile, circulating IgA-type anti-Pla2r antibodies were detected in a subset of cIgA-MN patients. Outcome analysis revealed comparable remission rates and progression to end-stage kideny disease between cIgA-MN and MN without IgA deposition. This study highlights clinical and pathological features of cIgA-MN, suggesting complex immune responses involving IgA in MN. IgA co-deposition did not significantly alter treatment responses or long-term outcomes.