Infection-related glomerulonephritis with IgA deposits, rarely reported in Europe,14,15 affects patients who present staphylococcal infection, hematuria, proteinuria and acute kidney injury with a proliferative glomerulonephritis at the biopsy. This presentation is comparable to that observed in American and Asian populations with some particularities in European patients. Moreover, the wide spectrum of both clinical presentation and histologic pattern can make the diagnosis challenging.16
Most affected patients are adult males aged 60 years. This finding is comparable to previous results reporting that 75–86% of the patients are male with a mean age of 55 to 65 years.9,10,13,17−21 It must be noticed that the youngest of our patients is a 5-year-old boy, meaning that IRGN-IgA, even if rarely reported, can be observed in pediatric patients. In our case and in other reported pediatric cases, children with Staphylococcus-related GN have the same presentation than adults, namely proteinuria and renal function impairment.22
Poststaphylococcal GN can occur in various immunocompromised background and poor prognosis is mainly linked to age and comorbidities.5,6 The initial description of Nasr et al. reported diabetic nephropathy in all biopsies. Nevertheless, the association between diabetes and IRGN-IgA is inconstant, reported in 8 to 55% of the patients in previous studies and in 44% of the patients in our study.10,13,17−19,23−25 As noticed since the first report, Staphylococcus represents the most frequent germ (78% in our study, 60 to 100% in other studies). A higher frequency of MRSA was observed in Asian and American studies (50 to 60%) compared to our cohort (15%). This observation is consistent with the low incidence of MRSA observed in France.26
Regarding the histological features of IRGN-IgA, we noticed some differences as compared to Asian and American studies. Most of them, but not all, reported mesangial proliferation, crescentic proliferation or fibrinoid necrosis in the same proportion. In our study, endocapillary proliferation (89% vs 23–63% in previous series) made of neutrophils in most cases (81% vs 15 to 63% of the biopsies) was more frequent whereas pure mesangial proliferation was less frequent compared to other studies.9,10,13,18,19,21 We also noticed differences when we compared histological patterns as classified in acute, subacute and resolving by Haas et al. in 2008.13 The authors reported more resolving and less acute or subacute patterns compared to our cohort, with 15% of acute, 23% of subacute and 62% of resolving GN vs 26%, 63% and 11% respectively in our cohort. Since we observed that the mean time from clinical onset of infection to renal biopsy increased with histological pattern from acute to resolving GN, one explanation could be a shorter delay between infection and renal biopsy in French centers (mean of 54 days for our patients, no data for other studies). The relation between the infection-to-biopsy delay and histological pattern supports the concept that these patterns represent different evolving aspects of the same disease. Never previously analyzed in IRGN-IgA, C4d deposits were observed in 65% of our biopsies. Diffuse and global (C4d 2+) staining was observed in biopsies with proliferative pattern (acute and subacute), and with shorter delay between infection and biopsy assessment, in favor of the activation of the complement pathway during the active phase of infection.
Regarding deposits, in addition to subepithelial “humps” deposits which are commonly described in IRGN-IgA, we also observed large subendothelial deposits with hyaline thrombi in 11% of the biopsies. These deposits are rarely encountered but were previously reported by Satoskar et al. in one biopsy.19
IRGN-IgA is a renal disease with poor prognosis. According to the literature data, risk of hemodialysis varies from 8 to 100% of the patients, risk of end-stage renal disease from 20 to 80% of patients, and risk of death reaches 30%.5,11,13,19,21 In our study, 33% of the patients required hemodialysis during acute phase of GN, 15% of the patients progressed to an end-stage renal disease, and 23% died. Previous studies did not show correlation between histologic pattern and renal prognosis, even though some authors observed that patients with renal recovery had less frequent acute tubular injury, interstitial inflammation or IF/TA.5,19 Our results confirmed the association between severity of IF/TA and renal prognosis in French patients. We did not find any correlation between other histological features or histologic patterns and renal outcome.
Regarding treatment, 10 patients (37%) in our study received corticosteroids in addition to antibiotics, without significant improvement of renal outcome. The use of corticosteroids remains controversial. For some authors,27 steroids may have a place in the treatment of patients who fail to respond to antibiotic therapy or patients with crescentic proliferation, whereas for other authors28 it can be deleterious in this form of GN in which infection is often ongoing.