Clinicopathological and prognostic study of IgA-dominant postinfectious glomerulonephritis

Background The clinicopathological and prognostic features of IgA-dominant postinfectious glomerulonephritis and its difference from the primary IgA nephropathy remains to be investigated. Methods The clinical and pathological data of 6542 patients who underwent renal biopsy from 2009 to 2020 in our hospital were reviewed and 50 patients who met the selection criteria of IgA-dominant postinfectious glomerulonephritis were enrolled to conduct a retrospective and observational single-center study. The selection criteria were: meet the characteristics of IgA dominance or codominance in immunofluorescence, and conform to 3 of the following 5 criteria: 1.Clinical or laboratory evidence show that there is infection before or at the onset of glomerulonephritis; 2.The level of serum complement decreased; 3.Renal pathology is consistent with endocapillary proliferative glomerulonephritis; 4. Glomerular immunofluorescence staining showed complement C3 dominance or codominance; 5. Hump-like subepithelial immune complex deposition was observed under electron microscopy. According to age, sex, renal function (estimated glomerular filtration rate, eGFR) and follow-up time, the control group was constructed with 1:3 matched cases of primary IgA nephropathy. The clinicopathological and prognostic differences between the two groups were analyzed. Results The most common histological pattern of IgA-dominant postinfectious glomerulonephritis was acute endocapillary proliferative glomerulonephritis and exudative glomerulonephritis. Immunofluorescence showed mainly IgA deposition or IgA deposition only, mainly deposited in the mesangial area (deposition rate 100 %), with typical C3 high-intensity staining (intensity++~+++), mainly deposited in the mesangial area (deposition rate 92.0 %). The fluorescence intensity of kappa is usually not weaker than lambda. The probability of the appearance of typical hump-like electron deposition under electron microscopy is low. Compared to primary IgA nephropathy, patients with IgA-dominant postinfectious glomerulonephritis had higher proportion of crescents (p = 0. 005) and endocapillary hypercellularity (p < 0.001) in pathological manifestations. Using serum creatinine level doubled of the baseline or reached end-stage renal disease as the endpoint, the prognosis of IgA-dominant postinfectious glomerulonephritis patients was worse than that of primary IgA nephropathy patients (p = 0.013). Conclusions The clinicopathological features of patients with IgA-dominant postinfectious glomerulonephritis was different from that of primary IgA nephropathy, and the prognosis was worse.

The severity of glomerular endothelial cell injury is associated with infiltrating macrophage heterogeneity in endocapillary proliferative glomerulonephritis

Endocapillary proliferation occurs in various types of glomerulonephritis (GN), with varying prognoses. We examined 42 renal biopsy samples representing endocapillary proliferative lesions from post-streptococcal acute GN (PSAGN), Henoch–Schönlein purpura nephritis (HSPN), and lupus nephritis (LN). In PSAGN, the glomerular capillary network was maintained, although severe lesions displayed dots or short, curved lines, indicating CD34-positive capillaries and suggesting capillary obstruction. Conversely, patients with LN and HSPN displayed obstruction of CD34-positive capillaries with dissociation from the glomerular basement membrane even in mild lesions. According to computer-assisted morphologic analysis, the cell density did not differ between the diseases. However, in PSAGN, the number of capillary loops was significantly increased, with a larger glomerular capillary luminal area than in the other groups. In addition, the number and frequency of CD163-positive cells (M2 macrophages) tended to be higher in PSAGN, while there were no significant differences in the number of CD68-positive (total) macrophages. These results indicate that in PSAGN, endothelial cell damage is less severe, and angiogenesis may be promoted. The severity of endothelial cell injury in each disease may be associated with differences in infiltrating inflammatory cell phenotypes.

Urinary sediments could differentiate the endocapillary proliferative lupus nephritis and endocapillary proliferative IgA nephrology

Background: The role of manual urine sediment examination in the diagnosis and prognostication of endocapillary proliferative glomerulonephritis remains to be elucidated. This study aims to investigated the differences of urinary sediment findings between lupus nephritis and IgA nephropathy with endocapillary proliferative glomerulonephritis and further evaluated associations of leukocyturia with disease activity, pathological features and prognosis.Methods: The urinary sediment of 126 patients, including 92 patients with lupus nephritis and 34 patients with IgA nephropathy, with a renal biopsy-proven endocapillary proliferative glomerulonephritis were examined in the morning before renal biopsy according to a standardized method. The urinary elements investigated including various cells, casts and crystals. The associations of the level of leukocyturia and disease activity, pathological features and prognosis were further analyzed.Results: In the patients with endocapillary proliferative glomerulonephritis, normal to mild leukocyturia (≤12/HPF), and moderate to severe leukocyturia (>12/HPF) were found in 52(41.27%) and 74 (58.73%) patients, respectively. The proportion of moderate to severe leukocyturia, the frequency of urinary white blood cells casts and waxy casts were significantly higher in endocapillary proliferative lupus nephritis patients compared with endocapillary proliferative IgA nephropathy patients (P<0.001, P=0.020, P=0.010, respectively). In the proliferative lupus nephritis group, the levels of leukocyturia was significantly correlated with serum creatinine (r=0.288, P=0.005), eGFR (r=-0.284, P= 0.006), serum C3 (r=-0.275, P= 0.009) , SLEDAI scores (r=0.383, P=＜0.001) and glomerular leukocyte infiltration (r=0.285, P= 0.002). A multivariate analysis showed that leukocyturia was identified as an independent risk factor for renal outcome in proliferative lupus nephritis (HR: 1.456, 95% CI: 1.083-1.957, P=0.013) but not in IgA nephropathy (HR: 1.069, 95% CI: 0.494-2.312, P=0.866).Conclusions: Urinary sediments of the endocapillary proliferative lupus nephritis and endocapillary proliferative IgA nephrology differed in many aspects. Leukocyturia could reflect the disease activity and prognosis of endocapillary proliferative glomerulonephritis, especially in lupus nephritis.

Clinicopathologic Features of Infection-Related Glomerulonephritis with IgA Deposits: a French Nationwide Study

Background: Infection-related glomerulonephritis with IgA deposits (IRGN-IgA) is a rare disease but it is increasingly reported in the literature. Data regarding epidemiology and outcome are lacking, especially in Europe. We aimed to assess the clinical, pathologic and outcome data of IRGN-IgA. Methods: Clinical and outcome data from patients from 11 French centers over the 2007-2017 period were collected retrospectively. We reviewed pathologic patterns and immunofluorescence of renal biopsies and evaluated C4d expression in IRGN-IgA. We analyzed the correlation between histological presentation and outcome. Results: Twenty-seven patients (23 men, mean age: 62±15 years) were included. Twenty-one (78%) had Staphylococcus aureus infection and twelve (44%) were diabetic. At the time of biopsy, 95.2% had haematuria, 48.1% had a serum creatinine level of >4 mg/dL, and 16% had hypocomplementemia. The most common pathologic presentation included mesangial (88.9%) and endocapillary proliferative glomerulonephritis (88.9%) with interstitial fibrosis and tubular atrophy (IF/TA) (85.1%). Diffuse and global glomerular C4d expression was found in 17.8%, mostly in biopsies with acute or subacute patterns, and was associated with a short delay between infection and renal biopsy compared to segmental and focal staining. After median follow-up of 13.2 months, 23.1% died, 46.2% had persistent renal dysfunction and 15.4% reached end-stage renal disease. Renal outcome was correlated to IF/TA severity. Conclusions: Infection-related glomerulonephritis with IgA deposits is usually associated with Staphylococcus infections and mainly affects adult men. This entity has a poor prognosis which is correlated to interstitial fibrosis and tubular atrophy severity.

Clinical features and outcome of infection-related glomerulonephritis with IgA deposits

Background Infection-related glomerulonephritis with IgA deposits (IRGN-IgA) is being more widely recognized but the precise epidemiology and outcome is lacking, particularly in Europe. We aimed to assess clinical, pathologic and outcome data of IRGN-IgA. Methods Clinical and outcome data from patients from 11 French centers over the 2007-2017 period were retrospectively collected. We reviewed pathologic patterns and immunofluorescence of renal biopsies and evaluated C4d expression in IRGN-IgA. We analyzed correlation between histological presentation and outcome using the Chi square test (qualitative data) and Kruskal-Wallis test (quantitative data). Results Twenty-seven patients (23 men, mean age: 62 ± 15 years) were included. Most of them had a Staphylococcus aureus infection (77.8%) and 44.4% were diabetic. At the time of biopsy, 95.2% had haematuria, 48.1% had a serum creatinine >4 mg/dL, and 16% had a hypocomplementemia. The most common pathologic presentation included mesangial (88.9%) and endocapillary proliferative glomerulonephritis (88.9%) with interstitial fibrosis with tubular atrophy (IF/TA) (85.1%). Diffuse and global glomerular C4d expression, found in 17.8% of the cases, was most frequently observed in biopsies with acute or subacute pattern and associated with a shorter delay between infection and renal biopsy compared to segmental and focal staining. After a median follow-up of 13.2 months, 23.1% died, 46.2% had persistent renal dysfunction and 15.4% reached end-stage renal disease. Renal outcome was correlated to IF/TA severity. Conclusions Infection-related glomerulonephritis with IgA deposits is usually associated with Staphyloccus infections and mainly affects adult men. This entity has a poor prognosis which is correlated to interstitial fibrosis and tubular atrophy severity.

Case of immunotactoid glomerulopathy showing high responsiveness to steroids therapy despite severe pathological features

A 72-year-old woman presented with nephrotic proteinuria and moderate haematuria. Renal pathology was compatible with immunotactoid glomerulopathy (ITG), for which there is no consensus for appropriate therapy. We, therefore, postponed immunosuppressive therapy. After 4 years, the patient’s renal function started to decline and renal pathology was re-evaluated, revealing a pathological change from mesangial proliferative glomerulonephritis to endocapillary proliferative glomerulonephritis. Treatment with oral prednisolone (30 mg/day) was initiated. Within 5 weeks, complete remission of proteinuria was obtained (proteinuria 6.02 g/gCr to 0.12 g/gCr), and the patient’s renal function stabilised. Generally, responsiveness to immunosuppressive therapy is poor in patients with ITG, and the present case represented a very rare clinical course. Some previous cases have indicated susceptibility to the therapy, regardless of the severity of renal damage. As a possible distinct entity that determines susceptibility to immunosuppressive therapy, we suggest the presence of a latent lymphoproliferative disease with no significant haematological symptoms.

Rapid and Complete Remission of Class IV Lupus Nephritis with Massive Wire Loop Lesions

Class IV lupus nephritis (LN) often has a poorer prognosis than other classes. However, class IV LN has various phenotypes, including not only segmental and global types but also others. We present the case of a 29-year-old woman with class IV-G LN who had an early response to glucocorticoid monotherapy. In addition, multiple lung nodules such as miliary tuberculosis (TB) were detected on computed tomography. All cultures of sputum, gastric fluid, and bone marrow were negative. A kidney biopsy revealed diffuse endocapillary proliferative glomerulonephritis with marked subendothelial deposition. Electron microscopy revealed massive electron-dense deposits in the subendothelial area, mesangium area, and peritubular capillaries. The histological diagnosis was class IV-G (A) LN. We administered high-dose glucocorticoid monotherapy. After treatment, the LN and the lung lesions had complete, rapid remission for 1 month. The lung lesions were associated with an immune complex similar to wire loop lesions, not TB. Thus, it is important to consider class IV-G LN with massive wire loop lesions as a new subtype.

Nephrotic Syndrome without Hematuria due to Infection-Related Glomerulonephritis Mimicking Minimal-Change Disease in a Child

Nephrotic syndrome without hematuria due to infection-related glomerulonephritis is uncommon. The present report describes a case of nephrotic syndrome due to infection-related glomerulonephritis without hematuria and hypertension in an older child. A 14-year-old boy was referred to our hospital because of a 5-day history of fever, nausea, weight gain and recent leg edema without hypertension. Laboratory data showed nephrotic-range proteinuria, hypoalbuminemia, mild hypocomplementemia and acute renal injury without hematuria. Although, due to the clinical presentation, minimal-change nephrotic syndrome was mostly suspected, a renal biopsy showed endocapillary hypercellularity mainly of mononuclear cells with segmental mesangiolytic changes. Fine granular IgG and C3 deposits were noted by an immunofluorescent study; many relatively small electron-dense deposits were observed electron-microscopically. These findings led to the diagnosis of nephrotic syndrome due to infection-related endocapillary proliferative glomerulonephritis, although the causative organism of his nephritis was not detected. He recovered with rest and dietary cure. When we examine an acute nephrotic child, infection-related glomerulonephritis should be considered as the differential diagnosis to avoid unnecessary use of corticosteroids.