**1. Introduction**

IgA vasculitis (IgAV), formerly known as Henoch–Schönlein purpura, is a systemic immune complex-mediated, small-vessel leukocytoclastic vasculitis. It is characterized by nonthrombocytopenic palpable purpura and/or arthritis, and abdominal pain [1]. IgAV, the most common vasculitis in children, is often a self-limiting and benign disease that spontaneously resolves.

A minority of pediatric IgAV patients exhibits kidney involvement—IgAV with nephritis (IgAVN)—usually 4–6 weeks after the onset of purpura [2–5]. The kidney-biopsy histopathologic features of IgAVN are similar to those of IgA nephropathy (IgAN), including glomerular IgA1-containing immunodeposits [1,2,4,6–11].

IgAV in adults has a more severe course and poor outcome due to the high frequency of glomerulonephritis, i.e., IgAVN—the most serious complication of this vasculitis. However, there is limited information about the histopathologic disease severity as related to disease onset.

**Citation:** Lai, L.; Liu, S.; Azrad, M.; Hall, S.; Hao, C.; Novak, J.; Julian, B.A.; Novak, L. IgA Vasculitis with Nephritis in Adults: Histological and Clinical Assessment. *J. Clin. Med.* **2021**, *10*, 4851. https://doi.org/ 10.3390/jcm10214851

Academic Editors: Kent Doi and Radica Alicic

Received: 2 September 2021 Accepted: 17 October 2021 Published: 22 October 2021

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In this study, we assessed the kidney histopathology and clinical and laboratory data in a large cohort of adult patients with IgAVN whose diagnostic kidney biopsies had been performed at different intervals after the onset of purpura.

#### **2. Materials and Methods**

#### *2.1. IgAVN Patients*

This is a retrospective study of 110 adult patients with IgAVN. All patients underwent a diagnostic kidney biopsy between 2002 and 2013 at the Department of Nephrology, Huashan Hospital, Fudan University, Shanghai, China. The diagnosis of IgAVN was based on the documented hematuria and proteinuria associated with a characteristic purpuric eruption, or abdominal or joint pain. IgA as the predominant mesangial immunoglobulin as per immunofluorescence microscopy in kidney biopsy specimens was required for inclusion in the study. We excluded patients whose biopsies contained <8 glomeruli, a number considered inadequate for appropriate histopathologic scoring (12), as detailed below.

The appearance of purpura defined the onset of IgAV. The 110 patients were divided into three groups based on the interval between purpura onset and diagnostic kidney biopsy: Group 1, <1 month (n = 14); Group 2, 1–6 months (n = 58); and Group 3, >6 months (n = 38; mostly >1 year, with the longest interval 13 years). All biopsies were performed for subjects who exhibited proteinuria in an outpatient setting (>0.5 g/24 h or urinary albumin/creatinine ratio >300 mg/g). The clinical features, laboratory data from the time of biopsy, and histopathologic findings in the biopsy specimens were retrospectively compiled for each group. However, no data from the outpatient follow-up visits since the onset of purpura or after kidney biopsy were available for this study. No personal identification information was collected. The study was approved by the ethics board of Huashan Hospital, Fudan University, Shanghai, China.

#### *2.2. Clinical and Demographic Data*

All clinical, laboratory, and demographic data were collected at the time of the kidney biopsy. The demographic data included age, gender, and comorbidities such as hypertension, diabetes mellitus, and cardiovascular disease. The characteristics of IgAVN included skin rash, gastrointestinal and joint manifestations, and kidney involvement. Proteinuria was evaluated by a 24-h urine measurement, hematuria was defined as 22 or more red blood cells (RBC) per microliter of urine (microscopic), or visible hematuria (macroscopic). The serum albumin, creatinine, urea nitrogen, uric acid, complement C3, and total IgA levels were measured at the time of kidney biopsy in the central clinical laboratory of Huashan Hospital. The number of urinary RBC had been determined by using a Sysmex UF-1000i analyzer (Siemens, Germany). Peripheral blood cell profiling was performed using a Sysmex xn-2000 analyzer (Siemens, Germany) and expressed as the total number of leukocytes and relative proportions of neutrophils and eosinophils (as % of total leukocytes).

## *2.3. Kidney Pathology*

Two pathologists examined and graded the histopathological changes. To evaluate the glomerular mesangial-cell proliferation, the cellularity of each glomerulus was graded as per the Oxford classification [12] (<4 mesangial cells/mesangial area = 0; 4–5 mesangial cells/mesangial area = 1; 6–7 mesangial cells/mesangial area = 2; >8 mesangial cells/mesangial area = 3), and a mean mesangial score was calculated for each biopsy. Mesangial Score: sum of grades divided by number of glomeruli (excluding globally sclerotic glomeruli). Crescents (%): number of glomeruli with crescents divided by number of glomeruli × 100. Leukocyte infiltration of glomeruli was considered significant when five or more polymorphonuclear and mononuclear cells per glomerulus were observed using the periodic-acid Schiff-stained tissue sections [11,12] (Figure 1).

**Figure 1.** Example of a glomerulus of a patient with IgAVN exhibiting mesangial proliferation and glomerular leukocytes. Representative leukocytes are marked by arrows. PAS stain, magnification 400×.

## *2.4. Statistical Analyses*

Normally distributed variables are expressed as the mean ± standard deviation (SD) and were compared using one-way analysis of variance (ANOVA) or Student's *t*-test. Nonnormally distributed variables are expressed as the median with interquartile range and were compared using the rank sum test. Categorical variables are expressed as percentages and compared using Pearson's chi-square test or Fisher's exact test. All tests were two-tailed, and statistical significance was defined as *p* < 0.05. The SPSS statistical software program (version 15.0, SPSS Inc., Chicago, IL, USA) was used for all analyses.
