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.

Role of clinicopathological features for the early prediction of prognosis in lupus nephritis.

Ambiguities remain regarding the role of clinicopathological characteristics in the early prediction of the prognosis of lupus nephritis (LN). Systemic lupus erythematosus (SLE) patients who completed routine follow-up were identified and retrospectively reviewed for eligible cases. Poor prognosis was defined as all-cause mortality or a persistent decrease of eGFR greater than half the baseline level or progression to end-stage renal disease (ESRD). An optimal Cox regression model was constructed for the early prediction of a poor prognosis for LN. Among the 2163 SLE patients, 376 eligible LN cases were enrolled in the study, with a median follow-up time of 55 [27.0, 87.0] months. The male-to-female ratio was 1:7.2, and 37 patients (9.8%) progressed to the composite endpoint. The ISN/RPS class was significantly associated with proteinuria levels (P-value < 0.001), and class IV/IV + V patients, but not class V patients, had the most severe proteinuria. Our optimal multivariate Cox regression model indicated that sex, ISN/RPS class, tubular atrophy/interstitial fibrosis, serum albumin, tertiles of proteinuria, and their interaction were independently associated with a poor prognosis. ROC analysis and external validation demonstrated that our model was efficient and robust for distinguishing LN patients with a poor prognosis. Our study constructed a robust and early predictive model for convenience in clinical practice to identify poor prognosis in LN patients. We found a significant interaction effect between proteinuria and serum albumin for the prediction of poor prognosis. LN patients with low-level proteinuria and hypoalbuminemia exhibit an increased hazard of progression to poor outcomes.

Clinical features and potential relevant factors of renal involvement in primary Sjögren's syndrome.

OBJECTIVE: To investigate distinct features of renal involvement in patients with primary Sjögren's syndrome (pSS) and to identify potential factors associated with renal involvement. METHODS: Four hundred and thrity-four pSS patients from the Rheumatology Department of the First Affiliated Hospital of Wenzhou Medical University from 2013 to 2017 were included in a cross-sectional study. Patients with renal involvement were compared with their age- and gender-matched controls (pSS without renal involvement). Demographic, clinical, histological, nephritic, immunological features of renal involvement in pSS were systematically analyzed. Possible factors related to renal involvement were identified using multivariate logistic regression analyses. RESULTS: One hundred and ninety-two pSS patients (88.48%) with renal involvement were women with mean age of nearly 58 years and mean disease duration of above 4 years. Clinical manifestation, serologic and immunological features and renal biopsy class of the pSS patients with renal involvement were presented. By multivariate analyses, xerophthalmia, histological positivity for lower salivary gland biopsy (LSGB), anti-SSA/Ro52-positive, reduced complement 3 (C3) levels, hypoalbuminemia and anemia retained significant association with renal involvement in pSS (all P < 0.05). CONCLUSION: In addition to LSGB pattern, anti-SSA/Ro52-positivity, reduced C3 levels, hypoalbuminemia and anemia, also indicate significant association with renal involvement in pSS. Therefore, early vigilance is required for patients with these clinical manifestations.

Renal outcomes in primary IgA nephropathy patients with segmental glomerular necrosis: a case-control study.

The renal prognosis and treatment of primary IgA nephropathy (IgAN) patients with segmental glomerular necrosis (SGN) remain controversial. Patients with primary IgAN confirmed by renal biopsy were enrolled. Patients with SGN on renal biopsy were selected as the necrosis group, and a propensity score matching method was used to match a control group according to age, gender, weight, height and follow-up time. A total of 825 IgAN patients were enrolled in the present study. Seventy-three (8.8%) patients with SGN were selected as the necrosis group, and 292 patients without SGN were matched as the control group. Compared to the control group, a significantly increased serum fibrinogen level (3.97 g/L vs 3.54 g/L, P=.002) and proportion of patients with macroscopic hematuria (35.6% vs 14.7%, P<.001) was observed in the necrosis group. According to the new IgA pathological classification system, crescent formation was more pronounced in the necrosis group (P=.001). The average estimated glomerular filtration rate was obviously higher in the necrosis group and decreased more slowly during follow-up. However, the time-averaged urine protein-to-creatinine ratio remained low in the necrotic group, whereas it gradually increased in the control group. SGN suggests an active renal inflammatory state, but it was not an independent risk factor for a poor renal outcome in patients treated with immunosuppressive therapy. Furthermore, patients with SGN had a more stable renal function and low urinary protein excretion during follow-up, which may be attributable to aggressive immunotherapy.

Elevated serum fibrinogen level is an independent risk factor for IgA nephropathy.

BACKGROUND: IgA nephropathy is a primary cause of renal failure, and inflammation and renal fibrosis are the main mechanisms leading to kidney damage. The serum fibrinogen level is closely related to inflammatory states, but its relationship to the prognosis of IgA nephropathy (IgAN) is unclear. MATERIALS AND METHODS: 1053 patients diagnosed with IgAN after renal biopsy were enrolled from two Nephrology Departments. Demographic and clinical data and histopathological features were collected. The patients were divided into four groups (Q1-Q4) according to the serum fibrinogen levels at the time of renal biopsy, and the relationships of serum fibrinogen levels with other risk factors and the prognosis of IgAN were investigated. RESULTS: 672 patients with proven primary IgAN were included in this study, which included a median follow-up of 36 months. Patients with higher serum fibrinogen levels had elevated serum creatinine levels, 24-hour urinary protein, and blood pressure compared with patients with the lowest levels of serum fibrinogen as well as severe renal damage at the time of renal biopsy. Univariate and multivariate Cox regression analyses confirmed that the serum fibrinogen level at the time of renal biopsy was significantly related to the prognosis of patients with IgAN. CONCLUSIONS: In patients with IgAN, an elevated serum fibrinogen level at the time of renal biopsy is associated with poor renal outcomes, which suggests the need for more aggressive early interventions. Greater benefits of aggressive treatments were observed in patients with higher serum fibrinogen levels.

Comparison of prognostic, clinical, and renal histopathological characteristics of overlapping idiopathic membranous nephropathy and IgA nephropathy versus idiopathic membranous nephropathy.

Overlapping idiopathic membranous nephropathy (IMN) and immunoglobulin A nephropathy (IgAN) is rare. This study aims to investigate the unique prognostic, clinical, and renal histopathological characteristics of IMN+IgAN. This retrospective observational study included 73 consecutive cases of IMN+IgAN and 425 cases of IMN treated between September 2006 and November 2015. Prognostic and baseline clinical and histopathological data were compared between the two patient groups. Poor prognostic events included a permanent 50% reduction in eGFR, end-stage renal disease, and all-cause mortality. Renal histopathology demonstrated that the patients with IMN+IgAN presented with significantly increased mesangial cell proliferation and matrix expansion, increased inflammatory cell infiltration, and higher proportions of arteriole hyalinosis and lesions than the patients with IMN (all P < 0.05). Kaplan-Meier analysis showed that the patients with IMN+IgAN had significantly higher cumulative incidence rates of partial or complete remission (PR or CR, P = 0.0085). Multivariate Cox model analysis revealed that old age at biopsy and high baseline serum creatinine and uric acid levels were significantly associated with poor prognosis (all P < 0.05), and increased IgA expression correlated significantly with PR or CR (P < 0.05). The present study found that overlapping IMN and IgAN presents with unique renal histopathology and appears not to cause a poorer prognosis than IMN.

Risk factors of progressive IgA nephropathy which progress to end stage renal disease within ten years: a case-control study.

BACKGROUND: There were few related studies aiming to severe IgA nephropathy (IgAN) which could progress rapidly to end stage renal disease (ESRD) within ten years. To find valuable clinical or pathological factors and promising precautions is essential. METHODS: A single center case-control study was performed. Fifty ESRD patients with the primary cause of IgAN and a short renal survival time of less than ten years after diagnose were enrolled in the case group. One hundred IgAN patients with a renal survival time of more than ten years were enrolled in the control group. IgA Oxford classification scores, clinical data at baseline and during the follow-up were collected. Multivariate logistic regression was used to investigate factors associated with the development of ESRD. RESULTS: There were significant differences in baseline clinical data between these two groups, as well as the constituent ratio of Oxford MEST-score. Distinct differences were observed in time-average uric acid(TA-UA), time-average hemoglobin(TA-Hb), time-average albumin(TA-Alb), time-average total cholesterol(TA-TC) and time-average urinary protein(TA-P) during the follow-up. In multivariate logistic models, IgA Oxford score M1(OR = 5.10, P = 0.018) and eGFR(OR = 0.97, P = 0.039) at biopsy, TA-UA (OR = 2.06, P = 0.026) and TA-Hb (OR = 0.53, P = 0.022) during the follow-up were identified independent factors for developing ESRD. CONCLUSION: IgAN patients with pathological assessment of M1, low baseline eGFR, TA-Hb and high TA-UA were more likely to progress to ESRD, and should be paid more attention. Appropriate regulations of UA, Hb and urine protein after diagnose may be a promising treatment.

Mycoplasma penetrans infection is a potential cause of immunoglobulin A nephropathy: a new animal model.

AIM: A new animal model of immunoglobulin A nephropathy (IgAN) was made by infecting mice with Mycoplasma penetrans (Mpe). To examine the pathogenesis of IgAN induced by Mpe infection, tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and nuclear factor-kB (NF-kB) protein levels were compared among study groups. METHODS: To make an experimental IgAN animal model, mice were infected with Mpe, SP-4 medium or phosphate-buffered saline (PBS) via the urinary tract. To compare changes in the classical IgAN model, TNF-alpha and IL-6 RNA expression levels were measured using RT-PCR, and NF-kB protein was measured using EMSA. RESULTS: By producing a urinary tract infection with Mpe, we developed a new animal model of IgAN with a 100% success rate. There was no difference with the classical animal model. We also observed IgG deposition in 66.67% of the Mpe-infection group. Glomerular cell and mesangial matrix proliferation was greater in the Mpe-infection group than in the control groups (p<0.05). In the Mpe-infection and classical groups, TNF-alpha and IL-6 expression levels were much higher than in the control groups (p<0.01). NF-kB expression was much higher in the Mpe-infection group (p<0.05). CONCLUSIONS: We made a new IgAN animal model that will offer a new direction for IgAN research. The activation of inflammation factors was associated with the Mpe induction of IgAN.