**3. Results**

#### *3.1. Baseline Clinical Data at the Time of Kidney Biopsy*

IgAVN patients (n = 110) in this study had a mean age of 36.5 ± 16.0 years at the time of kidney biopsy and consisted of 50 males and 60 females (Table 1). All patients presented with cutaneous purpura on at least one occasion; purpura was associated with arthralgia in 30 cases (26%) and with arthralgia and abdominal pain in 31 cases (27%). At the time of kidney biopsy, proteinuria ≥0.30 g/24 h was detected in 105 patients (92%) and 73 patients had proteinuria ≥1 g/24 h (64%). Five patients with proteinuria ≥0.5 g/24 h originally measured in the outpatient clinic had proteinuria <0.30 g/24 h later on admission to the hospital for kidney biopsy, likely due to prior treatment with an angiotensin-converting enzyme inhibitor (ACEi) and/or angiotensin receptor blocker (ARB).

Microscopic hematuria was observed in 86 patients (78%). Hypertension was present in 23 patients (21%) and 4 patients (4%) had diabetes mellitus (DM). Seven patients (6%) had reduced kidney clearance function, with an eGFR <60 mL/min/1.73 m<sup>2</sup> as per the MDRD formula. Twenty-seven patients (25%) had received an ACEi and/or an ARB before kidney biopsy.


**Table 1.** Clinical characteristics of 110 patients with IgAVN.

Abbreviations: SD, standard deviation; CI, confidence interval; eGFR, estimated glomerular filtration rate; ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker.

#### *3.2. Kidney Histopathology and Kidney Function*

The light-microscopic features for this cohort are summarized in Table 2. The patients had a mean mesangial score of 1.1 (range 0.3–2.4); 18% exhibited segmental sclerosis; 3%, global sclerosis; 25%, glomerular adhesion; 20%, glomerular leukocytes; 43%, tubular atrophy; 40%, interstitial fibrosis; 39%, interstitial leukocytes; and 9%, crescents. Kidney function was worse in the subjects with crescents than in those without crescents (serum creatinine: 0.91 ± 0.43 mg/dL vs. 0.76 ± 0.20 mg/dL, *p* = 0.038; eGFR: 93 ± 32 mL/min/1.73 m<sup>2</sup> vs. 109 ± 28 mL/min/1.73 m2, *p* = 0.009).

**Table 2.** Summary of the kidney pathology findings for 110 patients with IgA vasculitis with nephritis.


Abbreviations: CI, confidence interval.

*3.3. Histopathology of Kidney Biopsy Specimens with Different Intervals between Purpura Onset and Diagnostic Kidney Biopsy*

We next assessed whether the kidney pathology findings differed based on the interval between purpura onset and diagnostic kidney biopsy. The MEST-C scores (12) were calculated (Table 3). Using ANOVA and Student's *t*-test, the only significant difference between the groups was for M1 between Group 2 and Group 3 (*p* = 0.006). Furthermore, glomerular leukocytes were more common in Group 1 (57%) compared to Group 2 and Group 3 (*p* = 0.0008) (Table 3). Thus, IgAVN patients with kidney biopsy less than one month after purpura onset more frequently had leukocytes in the glomeruli. Furthermore, M1 was more common in Group 3 than in Group 2.

#### *3.4. Neutrophils in Peripheral Blood in Patients with Different Intervals between Purpura Onset and Diagnostic Kidney Biopsy*

Patients in Groups 1, 2, and 3 had a similar age, gender representation, mean 24-h proteinuria, hematuria, mean eGFR, and frequency of ACEi/ARB treatment. However, the percentage of neutrophils in the circulating leukocytes differed between groups (Group 1: 71 ± 8%; Group 2: 68 ± 11%; and Group 3: 60 ± 12%; *p* = 0.001), being the highest in patients biopsied within a month after onset of purpura (Table 3). When we evaluated the neutrophils to lymphocytes ratio (NLR), there was no significant difference for any comparison of the groups (Table 3).

**Table 3.** Characteristics of 110 patients with IgAVN grouped based on the interval between purpura onset and diagnostic kidney biopsy.


a 110 cases were divided into three groups: Group 1, <1 month; Group 2, 1–6 months; and Group 3, >6 months. b Fisher's Exact for proportions. c Abbreviations: yr, years; SD, standard deviation; SCr, serum creatinine; CI, confidence interval; eGFR, estimated glomerular filtration rate; ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; NLR, neutrophils to lymphocytes ratio; RBC, red blood cells; WBC, white blood cells (leukocytes) in peripheral blood. MEST-C scores were determined as described previously (12). M: mesangial hypercellularity; E: endocapillary hypercellularity; S: segmental glomerulosclerosis; T: tubular atrophy/interstitial fibrosis; C: cellular/fibrocellular crescents.

#### *3.5. Association of Serum Total IgA Concentration and Mesangial Proliferation*

The serum total IgA concentration positively correlated with the glomerular mesangialproliferation score (*p* = 0.0056) (Figure 2).

**Figure 2.** Glomerular mesangial proliferation correlates with serum total IgA level. Serum total IgA levels correlate with the mesangial proliferation score in patients with IgAVN. The line shows a linear fit (*p* = 0.0056).
