Primary IgA Nephropathy Research Articles

Clinicopathological feature analysis of IgA nephropathy complicated with acute kidney injury in children

Objective To investigate the clinicopathological features of IgA nephropathy(IgAN) complicated with acute kidney injury (AKI) in children. Methods The clinical and pathological data of children with biopsy-proven primary IgAN and complicated with AKI from January 2012 to December 2016 in the First Affiliated Hospital of Zhengzhou University were analyzed retrospectively, and the data of macroscopic hematuria (MH) associated AKI(15 cases) and other MH without AKI(99 cases) were compared. Results (1) Among 211 patients diagnosed with IgAN, 21 (9.95%) patients were complicated with AKI.Among the 21 cases, the average age was (9.5±2.1) years old, in which 17 cases(80.9%) were males, 19 cases with MH, and the range of the peak serum creatinine was 93-627 μmol/L.In histology, cellular/fibrocellular crescents were found in 11 cases, while high proportion of tubules filled with red blood cell(RBC) casts were observed in 8 cases, and moderate to severe acute tubular injury (ATI) were observed in 16 cases.In 2 cases, extensively mixed inflammatory cell infiltration with eosinophils was present in the interstitium.(2) According to the clinical and pathological characteristics, the 21 cases were divided into 3 groups: 15 cases with MH related AKI, 4 cases with crescentic glomerulonephritis, and 2 cases with acute interstitial nephritis.Compared with MH without AKI group(99 cases), the MH associated AKI group(15 cases) had significantly longer duration of MH, higher proteinuria level, urinary levels of β2-microglobulin (β2-MG) and N-acetyl-β-D-glucosaminidase (NAG), and greater frequency of RBC casts and ATI, and the differences were statistically significant(all P<0.05). In 2 acute interstitial nephritis cases, one had a history of taking weight loss drug with unknown ingredients, while the specific cause of the other was not clear.(3) None of the patients was on dialysis, but corticosteroid was prescribed in 17 cases (including methylprednisolone pulse therapy in 6), and 3 cases were combined with cyclophosphamide.Almost all patients achieved normal renal function except for one who had no response within 2 months after treatment.The median follow-up period was 24 months, in which 1 patient with crescentic glomerulonephritis progressed to end-stage renal disease. Conclusions AKI is commonly seen in children with IgAN, and complete recovery of renal function was seen in all patients with MH associated AKI and acute interstitial nephritis. Key words: IgA nephropathy; Acute kidney injury; Macroscopic hematuria; Child

"Associated" or "Secondary" IgA nephropathy? An outcome analysis.

BackgroundWhether differences in outcome between primary (pIgAN) and secondary IgA nephropathy (sIgAN) exist is uncertain.MethodsWe conducted a retrospective, observational study that included all histologically diagnosed IgAN patients between 2010–2017 (N = 306), 248 with pIgAN and 58 with sIgAN. To obtain samples with similar risk of progression, sIgAN patients were grouped as liver disease and autoimmune/viral disease and propensity score matched to corresponding pIgAN samples. Univariate (Kaplan Meier) and multivariate time-dependent (Cox modelling) analyses were performed to identify predictors of the composite end-point (doubling of serum creatinine, end-stage kidney disease or death).ResultsOf the whole cohort, 20% had sIgAN (6% alcoholic cirrhosis, 6% autoimmune disease and 8% viral infections). sIgAN patients were older, had more comorbidities, lower proteinuria and higher haematuria, but similar distribution in MESTC lesions and eGFR as those with pIgAN. They reached the end-point in similar proportions with those with pIgAN (43 vs. 30%; p = 0.09) but their mortality was higher (19 vs. 3%; p<0.0001). Both in unmatched (HR 0.80, 95%CI 0.42–1.52; p = 0.5) and matched samples (log-rank test: liver disease-IgAN vs. pIgAN, p = 0.1; autoimmune/viral-IgAN vs. pIgAN, p = 0.3), sIgAN was not predictive for end-point. In analyses restricted only to sIgAN, those with viral infections (HR, 10.98; 95% CI, 1.12–107.41; p = 0.03) and lower eGFR (HR, 0.94; 95%CI, 0.89–0.98; p = 0.007) had a worse prognosis. Immunosuppression did not influence outcome.ConclusionsThe differences in MESTC score and outcome between pIgAN and sIgAN seems to be minimal, suggesting that “associated” describes better than “secondary” the relationship among the two. Immunosuppression did not to influence outcome of sIgAN.

Plasma galactose-deficient immunoglobulin A1 and loss of kidney function in patients with immunoglobulin A vasculitis nephritis.

Immunoglobulin A (IgA) vasculitis nephritis (IgAV-N) is the most common secondary IgA nephropathy (IgAN). Many studies have demonstrated that galactose-deficient IgA1 (Gd-IgA1) in the IgA1 hinge region is associated with the development and also progression of primary IgAN. In this study, we aimed to evaluate the roles of Gd-IgA1 in kidney disease progression in a large Chinese cohort of IgAV-N patients. This cohort study enrolled 112 patients with IgAV-N, 15 patients with IgA vasculitis (IgAV) without kidney involvement and 108 patients with IgAN. Plasma IgA1 and Gd-IgA1 levels at kidney biopsy were measured by enzyme-linked immunosorbent assay. The primary endpoint was a 30% decline in estimated glomerular filtration rate or end-stage renal disease or death. The levels of Gd-IgA1 in IgAV-N and IgAN patients were higher than in healthy controls (mean ± SD, 302.86 ± 54.93 U/mL versus 303.16 ± 59.43 U/mL versus 281.30 ± 43.74 U/mL, respectively; P = 0.047), as well as compared with those with IgAV without kidney involvement (272.65 ± 53.14 U/mL; P = 0.036). After adjusting clinical data, higher levels of Gd-IgA1 were found to be independently associated with a greater risk for kidney failure [hazard ratio (HR) = 1.703 per 1 SD, 95% confidence interval (CI) 1.233-2.352; P = 0.001]. Compared with the first Gd-IgA1 quartile group (as reference), the fourth Gd-IgA1 quartile group retained a predictive value for poor renal outcome (HR = 3.740, 95% CI 1.204-11.619; P = 0.023). These data indicate that Gd-IgA1 levels were similarly elevated in adult patients with IgAN and those with IgAV-N. Moreover, increased Gd-IgA1 levels were associated with both the development and progression of IgAV-N, as observed in IgAN.

Immunostaining for galactose-deficient immunoglobulin A is not specific for primary immunoglobulin A nephropathy.

Primary immunoglobulin A nephropathy (IgAN) is characterized by IgA1-dominant or codominant glomerular deposits, postulated to be galactose deficient (Gd). However, glomerular IgA deposition can also occur in nonrenal diseases such as liver cirrhosis, psoriasis and inflammatory bowel disease ('secondary IgAN') or be an incidental finding in biopsies with other pathologies. A glomerulonephritis resembling IgAN can develop in patients with bacterial, mainly staphylococcal infections [staphylococcal infection-associated glomerulonephritis (SAGN)]. There are no specific histological features to distinguish between these, but differentiation is critical for appropriate management. The aim of this study was to investigate whether a recently described antibody to Gd-IgA1 (KM-55) could aid in differentiating primary IgAN from other conditions with glomerular IgA deposition, especially SAGN. We performed a retrospective cohort study of patients who underwent kidney biopsy for clinical indications and were found to have glomerular IgA deposits. We evaluated 100 biopsies, including primary IgAN (n = 44), secondary IgAN (n = 27), SAGN (n = 13), incidental IgA deposition (n = 8) and lupus nephritis (n = 8). There was no difference in Gd-IgA staining intensity or the proportion of positive cases between primary and secondary IgAN. SAGN and cases with incidental IgA deposits had significantly lower Gd-IgA staining intensity than primary IgAN, but up to 69% of SAGN cases were positive (albeit weaker). Gd-IgA staining is present not only in primary IgAN, but also in biopsies with secondary IgAN, SAGN and incidental IgA. Weak or negative staining may favor SAGN, especially in the setting of infection, or incidental IgA in the absence of nephritic symptoms or in the presence of other unrelated glomerular pathologies. However, positive staining for Gd-IgA alone is not specific enough for a diagnosis of primary IgAN.

Clinico-Epidemiological Profile of Primary IgA Nephropathy – An Institutional Experience in South India

Clinico-Epidemiological Profile of Primary IgA Nephropathy – An Institutional Experience in South India

A Study to Evaluate the Effectiveness and Safety of IONIS-FB-LRx, an Antisense Inhibitor of Complement Factor B, in Adult Participants With Primary IgA Nephropathy

A Study to Evaluate the Effectiveness and Safety of IONIS-FB-LRx, an Antisense Inhibitor of Complement Factor B, in Adult Participants With Primary IgA Nephropathy

SUN-033 IMPACT OF THE PRESENCE OF CRESECENTS ON DEVELOPMENT OF END STAGE KIDNEY DISEASE IN IgA NEPHROPATHY

Background: Oxford Classification of IgA nephropathy (IgAN) consists of the presence of 4 key pathologic features: mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S) and tubular atrophy and interstitial fibrosis (T). The association between MEST score and kidney outcome has been evaluated in previous studies. More recently crescents (C) were added to Oxford classification but the impact of crescents on prediction of renal outcome is less well studied. Aim: To evaluate the impact of crescents in kidney biopsy of patients with IgAN on development of end stage kidney disease (ESKD) and its’ interaction with other elements of Oxford classification as an independent variable. One- hundred fifteen patients with primary IgAN (76% men, mean age 37±13 years, mean serum creatinine: 2.7±2.1 mg/dl, and proteinuria: 3.4±2.5 g/24 hours) were followed for 43±29 months. Pathologic findings and MEST score were defined according to Oxford classification (M0/M1, E0/E1, S0/S1), but to increase the power of study, T was defined as T0<25% and T1≥ 25%. In this study crescents (C) were defined as C0 (absence) and C1 (at least one crescents in biopsy specimen). Association between Oxford classification scores and risk of ESRD were examined by time-dependent Cox model to estimate hazard ratio (HR) with 95% CI with univariate and multivariate analyses, which was adjusted for demographics, laboratory and pathological findings. Kaplan-Meier and the log-rank tests were used to estimate kidney survival. During follow-up 40 (35%) patients developed ESKD (dialysis or kidney transplantation). 44 (38%) patients had at least one crescent and among them 25 (57%) developed ESRD. From 57 (49.5%) patients with T1, 34 (60%) developed ESKD. Twenty-nine patients had bothT1and C1 and among them, 23 (79%) developed ESKD. In the adjusted model, the presence of T1+ C1 was associated with risk of ESKD (HR: 6.75, 95% CI 2.01-22.65, P<0.001), but this association was not significant for M1+C1, E1+C1 or S1+C1 (P=0.31, P=0.62, P=0.092, respectively). The median kidney survival was 80.8 months (95% CI, 75.0-86.7 months) for patients with T0+C0 and 27.3 months (95% CI, 16.1-38.3 months) for those with T1+C1. In this study on patients with IgAN who were pathologically classified with Oxford Classification, tubular atrophy and interstitial fibrosis≥25%, or the presence of at least one crescent in biopsy specimens, were independently associated with increased risk of developing ESKD. This risk was strongly increased in the presence of both C1+T1 and 80% of such patients developed ESKD in a mean period of 27 months, despite aggressive immunosuppressive therapy.

MON-043 Characteristics, immunosuppression and progression in IgA nephropathy with hyperuricemia

The aim of the study was to investigate clinicopathological characteristics, the role of immunosuppression and renal outcome in IgA nephropathy (IgAN) patients with hyperuricemia. We included 206 biopsy-proven primary IgAN patients between 2010 and 2015. The clinicopathological features, response to therapy, renal outcome and safety were recorded and analyzed. In univariate and multivariate models, hyperuricemia-associated pathological factors were analyzed. The patients with hyperuricemia presented higher systolic blood pressure, worse kidney function and more severe time-averaged proteinuria. Glomerulosclerosis, segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis and interstitial inflammation were worse in patients with hyperuricemia. By multivariate logistic regression analysis, only tubular atrophy/interstitial fibrosis (T1~2) (HR=3.969, 95% CI=1.439−10.945, P=0.008) was significantly associated with hyperuricemia, which was similar for IgAN patients with chronic kidney disease stage 1~2. For hyperuricemic patients, the response rate to therapy and renal survival rate were significantly higher in patients that received RAS blockade in combination with immunosuppression. Hyperuricemic IgAN patients presented more severe clinical characteristics. Tubulointerstitial injury could be a pathological feature closely related to hyperuricemia in IgAN. Immunosuppression could reduce proteinuria and improve renal outcome in IgAN patients with hyperuricemia.

Clinicopathological analysis for IgA nephropathy with isolated hematuria and/or mild proteinuria

To investigate the correlation of different types of urinary abnormalities or different proteinuria and hematuria with the pathological injury of kidney in IgA nephropathy with isolated hematuria and/or mild proteinuria. Methods: Patients with primary IgA nephropathy, isolated hematuria and/or mild proteinuria were enrolled in the Department of Nephrology, the Second Xiangya Hospital, Central South University from January 2013 to January 2018. According to the difference of red blood cell count in urinary sediment and quantitative of 24-hour urinary protein (24 h-UP) during renal biopsy, the patients were grouped in 3 ways: a simple hematuria group, a hematuria and proteinuria group, and a simple proteinuria group; a proteinuria I group, a proteinuria II group, and a proteinuria III group; a hematuria I group, a hematuria II group, and a hematuria III group. The clinical parameters such as age, mean arterial pressure, blood urea nitrogen, serum creatinine, blood uric acid, 24 h-UP, and renal pathological damage were compared. Results: A total of 157 patients met the inclusion criteria, including 71 males and 86 females. The most common pathological type was focal and/or segmental glomerulosclerosis. The Lee's classification were dominated by grade III and IV, and the renal pathological injury was heavy. Immunoglobulin deposition was dominated by simple IgA deposition. The most common fluorescence intensity of IgA deposition was +++. 97 (61.78%) patients were accompanied by complement deposition and were mainly composed of simple complement C3 deposition. There were 18 patients (11.47%) in the simple hematuria group, 111 patients (70.70%) in the hematuria and proteinuria group, and 28 patients (17.83%) in the simple proteinuria group. Compared with the simple hematuria group, the proportion of patients with mild injury was lower in the simple proteinuria group, and the proportion of patients with moderate-to-severe injuries was increased (χ2=7.053, P=0.008). Compared with the hematuria and proteinuria group, the proportion of patients with mild injury was lower in the simple proteinuria group, and the proportion of patients with moderate-to-severe injury was increased (χ2=4.294, P=0.038). Compared with the proteinuria I group, the proportion of patients with mild injury was lower in the proteinuria III group, and the proportion of patients with moderate-to-severe injury was increased (χ2=5.433, P=0.020). There was no significant difference in the proportion of patients with renal pathological injury among different hematuria groups (P>0.05). Conclusion: The clinical manifestations of patients with IgA nephropathy with hematuria and/or mild proteinuria are inconsistent with renal pathological damage. Some patients with mild clinical manifestations have severe renal pathological damage and the renal pathological damage is more serious in simple proteinuria. The more proteinuria, the heavier the renal pathological damage.

SP172Galactose deficient IgA1-specific monoclonal antibody is a useful tool for differentiation primary IgA nephropathy from secondary IgA nephropathy

SP172Galactose deficient IgA1-specific monoclonal antibody is a useful tool for differentiation primary IgA nephropathy from secondary IgA nephropathy

Impact of Induction Immunosuppression on the Recurrence of Primary IgA Nephropathy

ObjectiveThe objective of this study was to analyze the impact of induction immunosuppression on the incidence of recurrent IgA nephropathy (IgAN). MethodsWe conducted recurrence-free survival analysis of recipients of a first kidney transplant for IgAN who received a graft between 1995 and 2015. Kaplan-Meier and Cox regression analyses were used to sort the significant risk factors for recurrence. A total of 226 recipients with biopsy-proven IgAN received a kidney transplant, and 218 recipients were enrolled. ResultsAmong the recipients, 29 cases of IgAN recurrence were observed. The recipients were categorized into 3 groups according to induction immunosuppression: no induction (group 1, n = 72), anti-CD25 (group 2, n = 86), and antithymocyte globulin (ATG, group 3, n = 60). The 5- and 10-year cumulative IgAN recurrence rates were 9.7% and 21.0%, respectively. Recipients receiving ATG (group 3) exhibited significantly higher 4- and 5-year recurrence-free graft survival rates (both 96.4%) than recipients who received anti-CD25 (group 2, both 85.1%, P = .03). However, the induction therapy used (ATG or basiliximab) was not the risk factor for IgAN recurrence. ConclusionsTherefore, we concluded that ATG induction seems to postpone IgAN recurrence. These findings should be evaluated with well-designed prospective studies.

Significance of serum galactose deficient IgA1 as a potential biomarker for IgA nephropathy: A case control study.

BackgroundIgA nephropathy(IgAN) is a common glomerular disease with a higher risk of progression to end stage renal disease (ESRD) in certain ethnic populations. Since galactose deficient IgA1(Gd-IgA1) is a critical molecule in its pathogenesis, it has generated interest as a biomarker for this disease.MethodsWe measured serum Gd-IgA1 levels using a non- lectin based enzyme linked immunoassay(ELISA) in 136 immunosuppression naïve patients with primary IgAN and 110 controls(60-non IgA glomerular diseases, 50-healthy volunteers).ResultsMedian serum Gd-IgA1 levels were significantly higher in IgAN patients [13135.6(2723.3,59603.8)ng/ml] compared to those with non IgA glomerular disease [4954.8(892.9,18256.2) ng/ml] and healthy controls [6299.5(1993.2,19256) ng/ml] and this was observed even after log transformation and adjustment for age and gender(p<0.0001). Considering a cut-off value of serum Gd-IGA1≥7982.1ng/ml, the sensitivity for diagnosing IgAN compared to healthy controls was 74.3% and specificity was 72.0% with a positive predictive value of 87.8% and negative predictive value of 50.7%. The serum Gd-IgA1 level did not co-relate with baseline estimated glomerular filtration rate, urine protein creatinine ratio and the M, E, S, T and C scores on renal biopsy. The renal survival (absence of >30% decrease in eGFR, ESRD or death) was lower in patients with higher serum Gd-IgA1 levels(≥7982ng/ml) than those who had lower levels but it was not statistically significant(p = 0.486).ConclusionSerum Gd-IgA1 level is higher in IgAN patients compared to non-IgA glomerular diseases and healthy controls and has a good positive predictive value for diagnosis. However, it does not correlate with clinical and histological characteristics of disease severity and does not predict disease progression.

Steroid therapy in children with IgA nephropathy.

IgA nephropathy (IgAN) is one the most common primary glomerulonephritis in children and adolescents worldwide, with 20% of children developing end-stage kidney disease (ESKD) within 20years of diagnosis. There is a need for treatment guidelines, especially for steroids in children with primary IgAN, since the STOP-IgA trial casts doubts on the use of steroids in adults with intermediate risk. Pediatricians are prone to prescribe steroids in addition to renin-angiotensin system blockade (RASB) when proteinuria is > 0.5g/l, eGFR deteriorates < 70ml/min/1.73m2, or when a biopsy sample shows glomerular inflammation. Lack of randomized controlled trials (RCTs) in children with IgAN has led to an absence of consensus on the use of immunosuppressive agents in the treatment of progressive IgAN. This literature review evaluates the available evidence on steroid treatment in children with IgAN.

RETROSPECTIVE STUDY OF HISTOLOGICAL ANALYSIS AND ITS CORRELATION WITH CLINICAL PRESENTATION AND OUTCOME OF IGA NEPHROPATHY FROM A TERTIARY CENTRE OF GUWAHATI ASSAM.

Background: IgA nephropathy (IgAN) is one of the most common glomerular diseases with varied presentations. We aimed to study clinical presentation and outcome of IgAN and correlate with histopathology at the time of presentation.&#x0D; Methods: This is a retrospective study in which we analyzed kidney biopsy data, clinical manifestations and outcome of 137 patients with a diagnosis of primary IgAN from 2012 to 2016. Kidney biopsies were reviewed as per Oxford classification assessing mesangial hypercellularity, endocapillary hypercellularity, segmental sclerosis/adhesion, tubular atrophy/interstitial fibrosis. Correlation analysis was done for biopsy findings and clinical presentation/outcome. P score less than 0.05 was taken as significant.&#x0D; Results: Mean age for presentation was 27.35 years with 83 males and 54 females. Asymptomatic urinary abnormality was the most common clinical presentation (28.5%). Mean serum creatinine was 2.23 ± 2.06mg/dl with mean proteinuria of 1.49 ± 1.43g/day. Mesangial hypercellularity (M) and Endocapillary hypercellularity (E) lesions were significantly associated with proteinuria at the time of biopsy (p=0.02&amp; 0.04 respectively). Segmental glomerulosclerosis (S) and tubular atrophy (T) were significantly associated with eGFR and mean arterial pressure at the time of biopsy. Mean time of follow up was 1.6 years. M1, E0, S1, T0 were the most common lesions. M, S and T lesions in biopsy were significantly associated with decrease in GFR at the end of follow up.&#x0D; Conclusion: In our study, most common presentation of IgAN was AUA with rarity of macroscopic hematuria. M, S and T lesions were associated with decreased GFR on follow up.&#x0D; Key words: IgA Nephropathy, Nephrotic Syndrome, Oxford MEST classification

Predictive Capabilities of Three Widely Used Pathology Classification Systems and a Simplified Classification (Beijing Classification) in Primary IgA Nephropathy

Background/Aims: Several pathological classification systems were commonly used in clinical practice to predict the prognosis of IgA nephropathy (IgAN). However, how prognostic value differs between these systems is unclear. The aim of this study was to compare the Lee grade, the Oxford classification, and the Haas classification and to find a simplified classification. Methods: We retrospectively analyzed IgAN cases diagnosed between January 2002 and December 2007. The endpoints were progression to end-stage renal disease (ESRD) or a ≥50% decline in estimated glomerular filtration rate (eGFR). The predictive capabilities were evaluated by comparing the ability of discrimination (continuous net reclassification) and calibration (Akaike information criterion [AIC]). Results: A total of 412 IgAN patients were included in the study. The average follow-up period was 80.62 ± 23.63 months. A total of 44 (10.68%) patients progressed to ESRD, and 70 (16.99%) patients showed a ≥50% decline in eGFR. All multivariate Cox regression models had limited power for high AIC values. The prognostic values of the Lee grade and the Oxford classification were higher than those of models containing only established baseline clinical indicators for progression to ESRD or a ≥50% decline in eGFR (Lee grade 0.50, 95% CI 0.21–0.74; Oxford classification 0.48, 95% CI 0.28–0.71). The prognostic value of the Haas classification was lower than that of the other pathological classification systems for progression to ESRD or a ≥50% decline in eGFR (Lee grade 0.53, 95% CI 0.23–0.92; Oxford classification 0.59, 95% CI 0.10–0.74). The prognostic value of hierarchical classification (Beijing classification) using M and T lesion was similar to the Oxford classification. Conclusions: Both the Lee grade and the Oxford classification showed incremental prognostic values beyond established baseline clinical indicators. The Haas classification was slightly inferior to the Lee grade and the Oxford classification. The hierarchical classification (Beijing classification) using less pathological parameters does not lose predictive efficiency.

Crescents and Global Glomerulosclerosis in Chinese IgA Nephropathy Patients: A Five-Year Follow-Up

Background/Aims: This study aims to evaluate the clinical significance of crescent and global glomerulosclerosis formation on renal outcome in patients with IgA nephropathy (IgAN). Methods: Biopsy-proven primary IgAN patients from West China Hospital of Sichuan University were studied retrospectively between 2008 and 2015. Clinicopathological features and treatment modalities were recorded. The patients were divided into several groups on the basis of cellular and/or fibrocellular crescents scores and global glomerulosclerosis scores. Crescent (C) was scored according to the updated Oxford classification (C0/C1/C2). Global glomerulosclerosis (G) was scored according to the frequency of global glomerulosclerosis: G0 (≤25% of glomeruli), G1 (26–50% of glomeruli), and G2 (> 50% of glomeruli). The primary endpoint was defined as a 50% reduction in renal function or end stage renal disease. Patients were followed up for at least 12 months, or shorter if they reached study endpoints. 1328 patients with IgAN were recruited. Mean follow-up time was 46.1±23.6 months. The percentage of patients with C1 and C2 was 19.3% and 5.9% respectively. Higher crescent scores was associated with lower estimated glomerular filtration rates (eGFR), decreased serum albumin levels, increased amounts of urine protein, higher serum creatinine, as well as greater proportions of M1 and E1. The percentage of patients with G0, G1 and G2 was 70.5%, 20.7% and 8.8%, respectively. Elevated glomerulosclerosis scores were associated with lower eGFR levels, increased amounts of urine protein, higher levels of serum creatinine, higher incidences of arterial hypertension, as well as greater proportions of M1. There was a significantly higher proportion of T1/2 in patients with G2. In a multivariate model, crescent and global glomerulosclerosis were identified as independent predictors of decreased renal survival. Conclusion: Global glomerulosclerosis and crescents, as detected in renal biopsies, are strong predictors of long-term renal outcome of IgAN.

Analysis of the relationship between Oxford classification, IgM deposition and multiple indexes and the adverse prognosis of patients with primary IgA nephropathy and related risk factors.

The risk and influencing factors of prognosis in patients with primary IgA nephropathy (IgAN) were explored. One hundred and twenty-four patients who were diagnosed with IgA nephropathy in West China Hospital of Sichuan University were selected as the study subjects. The baseline data were recorded. All patients were followed up for 3 years. Patients with poor prognosis were defined as poor prognosis group, and the patient with no adverse prognosis was defined as a good prognosis group during the follow-up period. The risk factors that may affect the prognosis of patients with IgAN were analyzed by single factor analysis. The influence of all factors that were statistically significant on the prognosis of the patients was further evaluated by multifactor Cox regression. The single factor analysis and multivariate Cox proportional hazard model showed that patients with 24 h urinary protein, pathological type, Oxford classification (T1+T2), Lee (grade IV) and mesangial IgM deposition were independent factors of patients, and the difference was statistically significant, their P-values were 0.041, 0.046, 0.037, 0.043, and 0.028, respectively. Patients with 24 h urinary protein, pathological type, Oxford classification (T1+T2), Lee (grade IV) and mesangial IgM deposition can be used as independent factors affecting poor prognosis in primary IgAN patients. It provides evidence for early detection of high-risk IgA nephropathy.

Repeat renal biopsy improves the Oxford classification-based prediction of immunoglobulin A nephropathy outcome.

The prognosis of IgA nephropathy (IgAN) is very heterogeneous. Predicting the nature and the rate of the disease progression is crucial for refining patient treatment. The aim of this study was to evaluate the prognostic impact of an Oxford classification-based repeat kidney tissue evaluation to predict end-stage renal disease (ESRD). Patients with biopsy-proven primary IgAN who underwent two renal biopsies at our centre were analyzed retrospectively. Renal biopsies were scored by two pathologists blinded to the clinical data and according to the updated Oxford classification. Cox models were generated to evaluate the prognostic impact considering the Oxford classification elementary lesions from the first (Model 1) or the second (Model 2) biopsy, adjusted on clinical data at time of reevaluation. The prognostic impacts of the dynamic evolution of each elementary lesion between biopsies were also assessed through univariate and multivariate evaluation. A total of 168 adult patients were included, with a median follow-up duration of 18 (range 11-24) years. The second biopsy was performed either systematically (n = 112) of for-cause (n = 56), after a median time of 5.4 years. The prognostic performances of Model 2 (second biopsy) were significantly better than Model 1 (first biopsy, analysis of deviance P < 0.0001). The dynamic changes of C and T lesions were significantly associated with the progression toward ESRD after adjustment on variables from Model 2. Both static and dynamic Oxford-based histological evaluation offered by a repeat biopsy improves the prediction of ESRD in patients with IgAN.

Long-Term Outcome of Kidney Transplantation for IgA Nephropathy

Background Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, with a high recurrence rate after kidney transplantation (KTx). The aim of this study was to assess allograft survival, impact of recurrence on allograft function, and risk factors for post-transplant IgAN recurrence. Methods A total of 443 patients received KTx between March 1998 and August 2017 in Niigata University in Japan. We identified 104 patients with primary IgAN who underwent KTx and diagnosed recurrence of IgAN in 26 patients by graft biopsies. Graft biopsies were performed when urinary tests showed abnormal after KTx. Recurrence rate of IgAN, graft survival, the risk factors of recurrent IgAN and the results of treatment for recurrent IgAN were investigated. Results Median duration of follow-up was 119.5 months (1-259). Graft survival was not significantly different between the patients with primary IgAN compared with those with other primary diseases. IgAN recurrence rate at 1, 5, 10, and 20 years after KTx was 2 %, 16.5 %, 30.2 %, and 42.4 %, respectively. When graft survival was compared between the patients with IgAN recurrence and non-IgAN recurrence in the patients with primary IgAN, they were not significantly different (87.8 % vs 88.4 % at 10 years after KTx, respectively). The older age more than 30 y.o at KTx, the use of mycophenorate mofetil and basiliximab were associated with a lower risk of IgAN recurrence. Twenty patients underwent tonsillectomy and 24 patients received steroid pulse therapy (19 patients received both therapies). One patient didn’t receive any treatment for IgAN recurrence. Median follow-up period was 51 months (2-175) after treatment for IgAN recurrence. The improvement of mesangial IgA deposition showed in 6 out of 15 patients who underwent graft biopsy after treatment. Five patients (19.2 % in recurrent IgAN patients) lost their graft function due to IgAN recurrence during follow-up periods. Conclusions Recurrent IgAN remains a significant cause of graft loss in transplant recipients. Recipients with recurrent IgAN after KTx, especially younger patients, need to be followed up carefully.

Impact of Induction Immunosuppression on the Recurrence of Primary IgA Nephropathy

Purpose IgA nephropathy (IgAN) may recur after kidney transplantation (KT) and potentially jeopardize the survival of the graft. The object of this study was to analyze the impact of induction immunosuppression on the incidence of recurrent IgAN and identify predictive risk factors for IgAN recurrence. Methods We used data from the Samsung Medical Center to conduct a recurrence-free survival analysis of recipients of a first kidney transplant for IgAN who received a graft between 1995 and 2015. Kaplan-Meier and Cox regression analysis were used to sort the significant risk factors of recurrence. Two hundred twenty six recipients with biopsy-proven IgAN received aKT and 211 recipients were enrolled in this study. Among them, 30 cases of IgAN recurrence were observed. The recipients were categorized into four groups according to the induction immunosuppression: no induction (group 1, n=72), anti-CD25 (group 2, n=90), antithymocyte globulin (ATG, group 3, n=25), and ATG+anti-CD20 (group 4, n=24). Results Graft survival rate was lower in recipient with IgAN recurrence than those without recurrence. (p=0.001) The 5-year and 10-yearcumulative IgAN recurrence rates were 90.6% and 80.7%. Recipients received ATG (group 3) showed significantly higher 5-year recurrence free graft survival rate (100%) than recipients received no induction (group 1, 92.8%) or anti-CD25 (group 2, 85.0%). (p=0.02, <0.001, respectively). However, no significant risk factors for IgAN recurrence were identified with multivariate Cox regression analysis. Conclusion Recipients received ATG as induction immunosuppression showed low IgAN recurrence rate. However, the risk for IgAN recurrence was not associated with any specific induction immunosuppression modality. These findings should be further evaluated with well-designed prospective studies regarding the role of induction immunosuppression in reducing recurrence of IgAN.