Outcome Of IgA Nephropathy Research Articles

Renal outcome in IgA nephropathy according to Oxford classification and ultrastructural analysis in a Brazilian center .

Correlate clinical and histologic features with renal outcome in patients with biopsy-proven IgA nephropathy (IgAN). Retrospective analysis of records and renal tissue of IgAN patients. Histology was revised according to MEST score of Oxford classification. Focal segmental glomerulosclerosis (FSGS) features were assessed by light microscopy. Electron microscopy review searched for podocyte effacement. 67 patients were included, 56.7% men, mean age 34.5±12.5 years, mean arterial pressure (MAP) 106±18 mmHg, estimated glomerular filtration rate (eGFR) 63.32±43.07 mL/min/1.73m² and proteinuria 3.1±2.2 g/24 h. M1 was seen in 38 patients (56.7%), E1 in 12 (17.9%), S1 in 49 (73.1%), T1 in 18 (26.8%), and T2 in 17 (25.3%). Mean effacement index (EI) was 0.81±0.18 and did not correlate with proteinuria. 27 patients (40.2%) had end-stage renal disease (ESRD) which correlated with MAP (p = 0.002), eGFR (p = 0.0003), T1 (p = 0.0008) and T2 (p = 0.0001), follow-up MAP (p = 0.02) and follow-up proteinuria (p = 0.01 for 1.0-4.0 g/24 h and p = 0.005 for ≥4.0 g/24 h). T score correlated with MAP and proteinuria at baseline (p = 0.0001 and 0.0097, respectively) and during follow-up (p = 0.0001 and <0.0001, respectively). Podocyte hypertrophy correlated with MAP at baseline and during follow-up (p = 0.0046 and 0.0295, respectively). Tip lesion correlated with MAP at baseline (p = 0.0228). There was no correlation between FSGS features or EI with proteinuria or ESRD. Our data corroborate eGFR, proteinuria, MAP and T score as risk factors for ESRD in IgAN. Most patients had diffuse podocyte effacement, probably secondary to factors unrelated to proteinuria. .

Serum IgA/C3 and glomerular C3 staining predict severity of IgA nephropathy.

The aim of this study was to determine whether serum immunoglobulin A/complement factor 3 (IgA/C3) ratio and glomerular C3 staining predict outcome in IgA nephropathy. We collected data for 44 IgA nephropathy children treated with multi-drug combination therapy. The children were retrospectively divided into four groups based on serum IgA/C3 ratio and glomerular C3 staining: group A, IgA/C3 ratio >2.68 (median) and glomerular C3 staining ≥2.0, n=9; group B, IgA/C3 ratio >2.68 and glomerular C3 staining <2.0, n=7; group C, IgA/C3 ratio <2.68 and glomerular C3 staining ≥2.0, n=7; and group D, IgA/C3 ratio <2.68 and glomerular C3 staining <2.0, n=21. Clinical features; pathology at the first and second renal biopsy and at the latest follow up; and prognosis were analyzed for the four groups. At the most recent follow up, urinary protein excretion, incidence of hematuria, and serum creatinine in group A were all higher than in group D. At the second biopsy, crescent absence/presence ratio; mesangial hypercellularity, segmental glomerulosclerosis or adhesion, endocapillary hypercellularity, and tubular atrophy/interstitial fibrosis as well as crescents and global glomerulosclerosis (MESTCG) score; and clonicity index in group A were higher than in group D. All patients in group D had normal urine, and the prevalence of persistent nephropathy in group A was higher than in group D. Serum IgA/C3 ratio and glomerular C3 staining can predict outcome in IgA nephropathy.

A proposed Oxford classification-based clinicopathological nomogram for predicting short-term renal outcomes in IgA nephropathy after acute kidney injury

BackgroundThis study aimed to investigate the effect of acute kidney injury (AKI) on the progression of renal disease and to develop a clinico-pathological nomogram to predict the renal outcome of IgA nephropathy (IgAN) patients, based on Oxford classification score. MethodsThis is a retrospective observational study. A total of 988 IgAN patients treated at our hospital between 2006 and 2011 were included and divided into AKI (n = 82) and non-AKI group (n = 906). The primary outcome measure was the composite renal endpoint. The secondary outcome measure was all-cause mortality. Clinical and pathologic features were assessed with multivariable Cox regression to predict the outcome in IgAN patients. A nomogram was developed to predict the renal outcome. ResultsThe median follow-up time was 48.6 months (range: 34.4 to 62.7). The incidence of AKI was 8.30%. The AKI group had more severe pathological characteristics and a significantly poor survival outcome than the non-AKI group. The multivariate Cox regression analysis showed that the AKI group had a 2.84 times higher risk of the composite renal endpoint as compared with the non-AKI group (P < 0.001). A clinico-pathological nomogram was developed using the seven predictors for the primary renal composite endpoint. The AUC for the nomogram model was 0.81 (sensitivity = 0.78, specificity = 0.85), and the C-index was 0.91 (95% CI = 0.85–0.97). ConclusionsFor IgAN patients, AKI is an independent risk factor for the progression of renal disease. Our nomogram model has good prediction power for the renal outcome of IgAN patients.

Clinicopathological Characteristics, Role of Immunosuppressive Therapy and Progression in IgA Nephropathy with Hyperuricemia

Background/Aims: The aim of the study was to investigate clinicopathological characteristics, the role of immunosuppressive therapy and renal outcome in IgA nephropathy (IgAN) patients with hyperuricemia. Methods: 206 biopsy-proven primary IgAN patients were included between January 2010 and December 2015, and divided into two groups: patients without hyperuricemia (n=122), and patients with hyperuricemia (n=84). The clinicopathological features, response, renal outcome and safety were recorded. In univariate and multivariate models, hyperuricemia-associated pathological factors were analyzed. Results: The patients with hyperuricemia presented higher systolic blood pressure, worse kidney function and more severe time-averaged proteinuria. Proportions of glomerulosclerosis, segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis, lymphocytes and monocytes infiltration were higher, while the proportion of segmental adhesion was lower 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. For hyperuricemic patients, the response rate to therapy and renal survival rate were significantly higher in patients that received RAS blockade in combination with immunosuppressive therapy. After RAS blockade treatment, renal survival in the patients with hyperuricemia was worse compared with the patients without hyperuricemia. Conclusion: Hyperuricemic IgAN patients presented more severe clinical features. Tubulointerstitial injury could be a pathological feature closely related to hyperuricemia in IgAN. Immunosuppressive therapy and RAS blockade could reduce proteinuria and improve renal outcome in IgAN patients with hyperuricemia.

Mannose-Binding Lectin Levels Could Predict Prognosis in IgA Nephropathy.

IgA nephropathy (IgAN) is characterized by infections followed by episodic gross hematuria. Deficiency of mannose-binding lectin (MBL) is associated with recurrent infection in many diseases, but controversy exists regarding the role of MBL in IgAN. Here, we measured MBL2 variants and MBL levels in 749 patients with IgAN and 489 healthy controls. Overall, 5.2% (39 of 749) of patients with IgAN had MBL deficiency (MBL levels <100 ng/ml), among whom LYPB/LYPB and LXPA/LYPB were the predominant MBL2 haplotypes (82%; 32 of 39). We found a nonlinear association between MBL levels and renal outcome in IgAN. Patients with IgAN and MBL deficiency had a higher incidence of prodromic infections and gross hematuria than those with sufficient MBL levels (100-3540 ng/ml). Moreover, MBL deficiency independently associated with poor renal outcome in IgAN after multiple adjustments (hazard ratio, 5.18; 95% confidence interval, 2.50 to 10.72; P<0.001). Patients with high MBL levels (>3540 ng/ml) had more severe proteinuria and a higher proportion of crescents, although the association with IgAN progression did not reach statistical significance after adjustments. In conclusion, MBL deficiency and MBL excess may both have deleterious effects on IgAN progression, which suggests that MBL contributes to IgAN pathogenesis through multiple mechanisms.

Clinical outcomes of IgA nephropathy patients with different proportions of crescents.

Crescents involving more than 50% of glomeruli in IgA nephropathy (IgAN) signify a rapid deterioration of renal function. However, little is known about the prognosis of IgAN patients presenting crescents in less than 50% of glomeruli. We aimed to investigate the clinicopathological characteristics and outcomes of IgAN patients with different proportions of crescents.From January 2000 to December 2011, biopsy-proven primary IgAN patients with histological crescents formation were enrolled in this retrospective cohort study. The patients were divided into 4 groups on the basis of crescent proportion as follows: <5%, 5% to 9%, 10% to 24%, and ≥25%. The primary endpoint was defined as the doubling of baseline serum creatinine (SCr) and/or end-stage renal disease (ESRD), and the secondary endpoint was death.A total of 538 crescent-featured IgAN patients were followed up and included in the analysis. The median crescent proportion was 8.0%. An increasing crescent proportion was associated with a reduced estimated glomerular filtration rate (eGFR), decreased level of hemoglobin, and increased amount of urine protein excretion. After a median follow-up period of 51 months (range 12-154 months), the endpoint events-free survival rate of the above 4 groups were 69.9%, 47.7%, 43.8%, and 40.6%, respectively (Log rank=13.7, P= 0.003), when we incorporated death with renal outcome as a composite endpoint. Multivariate Cox regression analyses adjusting for eGFR, hypertension, proteinuria, and the Oxford-MEST classification demonstrated the predictive significance of an increasing crescent proportion with renal survival and mortality (each increase by 5% [log-transformed]: HR=1.51, 95% CI 1.08-2.11, P = 0.02). Further comparisons of patients with small proportions of crescents (<5%) and those absent of such pathological lesion showed that the 2 groups of patients had comparable prognosis.An increasing crescent proportion was identified as an independent predictor for unfavorable clinical outcomes in IgAN. Therefore, a small proportion of crescents, over 5% particularly, should be paid more attention in clinical practice.

A Systematic Review and Meta-Analysis of Kidney and Pregnancy Outcomes in IgA Nephropathy

Background: The outcomes of pregnancy in immunoglobulin A nephropathy (IgAN) remain controversial. We sought to evaluate the effect of pregnancy on the progression of IgAN as well as the impact of IgAN on pregnancy outcomes. Methods: We systematically searched MEDLINE, Embase for cohort or case-control studies. OR reductions were calculated with a random-effects model, and kidney outcomes and adverse pregnancy events were analyzed. Results: Our literature search returned 652 relevant articles; 4 studies were included, providing data of 376 pregnancies in 273 patients with IgAN and that of 241 IgAN who did not become pregnant. Four hundred sixty seven patients with chronic kidney disease stages 1-2 were included. Pregnancy in patients with IgAN did not increase the risk of adverse renal events including doubling of serum creatinine, 50% decline in glomerular filtration rate (GFR) and end-stage kidney disease (OR 0.97, 95% CI 0.55-1.70; p = 0.90; I² = 0.0%, p = 0.79). There was no significant difference in the change in estimated GFR at the end of follow-up in the pregnant and non-pregnant groups (weighted mean difference 0.1 ml/min/1.73 m² (95% CI -4.85 to 5.04 ml/min/1.73 m²), p = 0.97; I² = 0%, p = 0.95). Women with IgAN had high rates of infant loss (12.2, 7.4-19.4%), preterm delivery (8.5, 5.9-12.1%), low birth weight (9.5, 6.7-13.3%), and preeclampsia/severe preeclampsia (7.3, 4.9-10.6%). Conclusions: Pregnancy in IgAN patients with preserved kidney function did not accelerate deterioration of renal function. But pregnant women with IgAN are at higher risk of pregnancy complications.

Glomerular disease: Immunosuppressant-induced reduction of proteinuria in IgAN.

Time-averaged proteinuria (TAP) is thought to be the most reliable predictor of outcomes in IgA nephropathy (IgAN). New data suggest that corticosteroids reduce TAP and presumably improve outcomes in IgAN, but increase the risk of adverse effects. Whether TAP is a good surrogate end point for clinical trials remains unclear.

Outcomes of IgA Nephropathy with Segmental Glomerular Necrosis But without Crescent Formation

Background: The significance of segmental glomerular necrosis (SGN) was not evident in immunoglobulin A nephropathy (IgAN) patients. Especially, there were a number of patients who presented with slight histopathological damage except SGN. We, therefore, conducted a study to highlight the occurrence of these cases and to define their clinical characteristics and outcomes at our centre. Methods: The clinical, laboratory and pathological manifestations and outcomes of these IgAN patients were collected and compared with IgAN patients with simily histopathological background but without SGN. Survival curves were constructed according to the Kaplan-Meier method. Multivariate Cox regression analysis was used to identify independent factors for the development of endpoint. Results: Eighty-two patients with SGN but without crescents were found in Haas grades I-III. Macroscopic hematuria and prodromal infection were more popular and the mean daily proteinuria was significantly higher in patients with SGN. More patients had high serum IgA in the ecrotizing IgAN group. At last follow-up, there were no differences in hypertension, proteinuria, serum creatinine, estimated GFR and the incidence of end-point events between 2 groups. SGN was not an independent predictor for the prognosis of IgAN. Corticosteroid treatment could decrease proteinuria significantly. The outcomes of the 2 populations of necrotizing IgAN patients with or without corticosteroid treatment were not different. Conclusions: SGN can be found in mild pathological damage patients and is not always associated with crescent formation. Heavier proteinuria was found in these IgAN patients. SGN was not an independent predictor for the prognosis of IgAN.

NLRP3 Localizes to the Tubular Epithelium in Human Kidney and Correlates With Outcome in IgA Nephropathy.

Nod-like receptor pyrin domain-containing-3 (NLRP3) has been implicated in the pathogenesis of experimental renal injury, yet its characterization in human kidney disease remains largely unexplored. NLRP3 expression was evaluated in human kidney biopsies, primary renal tubular cells (HPTC) and correlated to disease outcomes in patients with IgA nephropathy (IgAN). NLRP3 localized to renal tubules in normal human kidney tissue and to mitochondria within HPTC by immunohistochemistry and immunofluorescence microscopy. Compared to control kidneys, NLRP3 gene expression was increased in biopsies of patients with IgAN. While NLRP3 expression in IgAN was detected in glomeruli, it remained largely confined to the tubular epithelial compartment. In vitro NLRP3 mRNA and protein expression were transiently induced in HPTC by TGF-β1 but subsequently diminished over time as cells lost their epithelial phenotype in a process regulated by transcription and ubiquitin-mediated degradation. Consistent with the in vitro data, low NLRP3 mRNA expression in kidney biopsies was associated with a linear trend of higher risk of composite endpoint of doubling serum creatinine and end stage renal disease in patients with IgAN. Taken together, these data show that NLRP3 is primarily a kidney tubule-expressed protein that decreases in abundance in progressive IgAN.

The role of tonsillectomy in IgA nephropathy.

The IgA nephropathy (IgAN) is a very common glomerulonephritis and can result in end-stage renal disease. From a clinical point of view, IgAN is characterised by repeated events of macrohaematuria associated with infections of the upper airways. In IgAN, the IgA released by the tonsillar lymphatic tissue into blood circulation are defective in glycosylation. These aberrant IgA can reach the glomeruli and deposit into mesangium causing an inflammation with cellular proliferation. The treatment is not yet well defined: steroids and immunosuppressive drugs are suggested in cases with a progressive disease. Tonsillectomy was proposed to reduce the infective events of upper airways and the lymphatic tissue producing undergalactosylated IgA. The experiences in literature coming from Asia report positive effects of tonsillectomy on IgAN. In patients with tonsillectomy, the renal signs improved (less haematuria and proteinuria) and the renal outcome was better (slower progression of renal damage). These were uncontrolled studies and tonsillectomy was associated with steroid and immunosuppressive treatment, so it is not possible to tell the real effect of tonsillectomy. In contrast, the European studies reported that the tonsillectomy was not associated with a better outcome of IgAN. A critical review of the subject reveals that most of the papers with positive results were uncontrolled retrospective experiences, while in a randomised controlled trial paper the advantages of tonsillectomy disappeared. In conclusion, this review, in agreement with the international guidelines, concludes that tonsillectomy does not play any role in the progression of IgAN.

Rs 2856717 Effect on the Clinical Manifestations and Poor Outcome of IgA Nephropathy

Rs 2856717 Effect on the Clinical Manifestations and Poor Outcome of IgA Nephropathy

Correlation of disease activity in proliferative glomerulonephritis with glomerular spleen tyrosine kinase expression

Spleen tyrosine kinase (SYK) is an important component of the intracellular signaling pathway for various immunoreceptors. Inhibition of SYK has shown promise in preclinical models of autoimmune and glomerular disease. However, the description of SYK expression in human renal tissue, which would be desirable ahead of clinical studies, is lacking. Here we conducted immunohistochemical analysis for total and phosphorylated SYK in biopsy specimens from >120 patients with a spectrum of renal pathologies, including thin basement membrane lesion, minimal change disease, membranous nephropathy, IgA nephropathy, lupus nephritis, ANCA-associated glomerulonephritis, antiglomerular basement membrane disease, and acute tubular necrosis. We found significant SYK expression in proliferative glomerulonephritis and that glomerular expression levels correlated with presenting serum creatinine and histological features of disease activity that predict outcome in IgA nephropathy, lupus nephritis, ANCA-associated glomerulonephritis, and antiglomerular basement membrane disease. SYK was phosphorylated within pathological lesions, such as areas of extracapillary and endocapillary proliferation, and appeared to localize to both infiltrating leucocytes and to resident renal cells within diseased glomeruli. Thus SYK is associated with the pathogenesis of proliferative glomerulonephritides, suggesting that these conditions may respond to SYK inhibitor treatment.

Role of immunosuppressive therapy and predictors of therapeutic effectiveness and renal outcome in IgA nephropathy with proteinuria.

IntroductionThe aim of the study was to analyze the role of immunosuppressive therapy and identify independent predictors of therapeutic effectiveness and outcome in IgA nephropathy (IgAN) patients with proteinuria.Material and methodsTwo hundred and six IgAN patients with proteinuria (1–3.5 g/day) were included between January 2005 and December 2011, and divided into two groups: group A (n = 125), receiving renin-angiotensin system blockade therapy alone; and group B (n = 81), combining the above with immunosuppressive therapy. The clinicopathological features, response and safety were recorded. In univariate and multivariate models, the factors that influence response to therapy and renal outcome, especially pathologic features, were analyzed.ResultsThe patients in group B presented more severe proteinuria and hypoalbuminemia with more severe hematuria (p < 0.05) but no significant difference in the pathologic changes compared with group A. After follow-up, the response rate was higher in group B than in group A (p < 0.001). No pathologic feature or clinical parameter apart from steroid therapy (HR = 0.500, 95% CI: 0.304–0.821, p = 0.006) was strongly associated with therapeutic effectiveness. Endocapillary hypercellularity (HR = 2.849, 95% CI: 1.244–6.524, p = 0.013) seemed to be an independent predictor of poor response to steroid therapy. The renal survival rate was not significantly different between the two groups (p = 0.074). Estimated glomerular filtration rate at baseline may be an independent predictor of renal outcome.ConclusionsSteroid therapy could be an effective therapy in proteinuric IgAN patients, and endocapillary hypercellularity seemed to predict poor response to steroid. Renal function at baseline rather than treatment strategies and pathologic features may be independently associated with renal survival.

Clinicopathological Features and Outcomes of IgA Nephropathy with Hematuria and/or Minimal Proteinuria

Background/Aims: Information regarding the clinical and histological prognostic factors of IgA nephropathy (IgAN) is mostly derived from patients in whom diagnostic renal biopsies were performed because their proteinuria levels were higher than 1-2 g/d. The clinicopathological features and outcomes of IgAN patients presenting with normal blood pressure, normal renal function, hematuria and minimal or no proteinuria are not well described. We therefore conducted a study of the clinicopathological features and outcomes in IgAN patients with these characteristics. Methods: The clinical, laboratory, and pathological manifestations and long-term outcomes of all IgAN patients with the above-mentioned characteristics were collected. The relationships between renal pathology, injury, long-term outcomes and clinical factors were studied, and the risk factors of IgAN were analyzed using multivariate logistic regression. Results: Of all of the renal biopsy cases, IgAN with the above features accounted for 8.9%. Among these patients, 67.2% (253) showed simultaneous hematuria and proteinuria, 23.1% (87) showed only hematuria, and 9.7% (36) showed only proteinuria. Additionally, 33.8% (127) patients showed macroscopic hematuria and 65.1% (245) had a prodromal infection. Regarding renal pathological changes, 45.5% (171) of the patients were unexpectedly classified as Grade II to IV (Hass classification). Proteinuria at the time of renal biopsy was an independent predictor of more severe renal pathological injury. After a median follow-up of 75 months, 61 (16.2%) patients experienced adverse events. Among these patients, 28 (7.45%) exhibited hypertension, 22 (5.85%) presented proteinuria levels >1 g/24 h, and 11 (2.9%) developed impaired renal function. Conclusions: Severe renal histological injury may be observed in some IgAN patients with benign clinical characteristics. Proteinuria is an independent predictor of severe renal pathological injury in IgAN patients with mild proteinuria. More severe pathological injury (> Grade II, Hass classification) are predictors of poor prognosis.

Effect of hematuria on the outcome of IgA nephropathy with mild proteinuria.

The effects of hematuria on the outcome of IgA nephropathy (IgAN) remain unknown and treatment of IgAN with severe hematuria is controversial. Eighty-eight IgAN patients with proteinuria <0.5 g/day and who had not received corticosteroids, immunosuppressive agents, or undergone a tonsillectomy were divided into two groups: (1) patients with low (<20/high-power field [HPF]) urinary red blood cell (U-RBC) counts (L-RBC group, n = 48); and (2) patients with high (≥20/HPF) U-RBC counts (H-RBC group, n = 40). Clinical and histological findings, renal survival rate and risk factors for progression were analyzed. The male ratio and blood pressure were significantly higher in the L-RBC group. Median proteinuria, mean estimated glomerular filtration rate and histological findings according to Oxford classifications were similar. During the 5 years after renal biopsy, the median amount of proteinuria remained at <0.5 g/day or g/g creatinine in both groups, and the median U-RBC decreased to <10/HPF in both groups without any intensive therapy. The 15-year renal survival rate, estimated using the Kaplan-Meier method, was 100 % in the H-RBC group, but decreased to 83.4 % in the L-RBC group, although it was not significant. The treatment of inhibitors of renin-angiotensin system (RAS inhibitors) decreased the risk for progression by Cox regression analysis (hazard ratio: 0.14, p = 0.027). Severe hematuria at the time of biopsy naturally improved without any intensive therapy, and there were no negative effects of hematuria on the outcome of IgAN with mild proteinuria. Its prognosis was relatively good, and the treatment of RAS inhibitors might prevent from progression.

Pathology of IgA nephropathy.

IgA nephropathy is defined by the presence of IgA-dominant or co-dominant immune deposits within glomeruli. Biopsy specimens meeting these diagnostic criteria have a range of histological changes that are reflected in the variable clinical course of IgA nephropathy. The impact of histology on outcomes in IgA nephropathy has been clarified in a number of large retrospective clinicopathological studies. These studies have consistently demonstrated that the stage of disease at presentation, as indicated by the extent of interstitial fibrosis and tubular atrophy in the biopsy, is the strongest histological predictor of renal survival. The effect of active proliferative lesions on the disease course is less clear cut, owing in part to considerable treatment bias in most published retrospective studies. There is evidence that endocapillary hypercellularity and cellular crescents are responsive to immunosuppressive therapy, but this observation requires confirmation in prospective randomized controlled trials. Future challenges include improving the reproducibility of histological scoring, particularly for the presence and extent of endocapillary lesions, and to improve prognostic modelling by combining histological data with clinical variables and biomarker data.

Association of C4d Deposition with Clinical Outcomes in IgA Nephropathy

Several studies have suggested that activation of the complement system is a contributing pathogenic mechanism in IgA nephropathy (IgAN). C4d staining is an inexpensive and easy-to-perform method for the analysis of renal biopsies. This study aimed to assess the clinical and prognostic implications of C4d staining in IgAN. This retrospective cohort study included 283 patients with IgAN in 11 hospitals in Spain who underwent a renal biopsy between 1979 and 2010. The primary predictor was mesangial C4d staining. Secondary predictors included demographic, clinical, and laboratory characteristics, and Oxford pathologic classification criteria. The primary end point was the cumulative percentage of patients who developed ESRD, defined as onset of chronic dialysis or renal transplantation. C4d was analyzed by immunohistochemical staining using a polyclonal antibody. Kaplan-Meier and Cox proportional hazards analyses were performed to evaluate the effect of C4d staining on renal survival. There were 109 patients (38.5%) and 174 patients (61.5%) who were classified as C4d positive and C4d negative, respectively. Renal survival at 20 years was 28% in C4d-positive patients versus 85% in C4d-negative patients (P<0.001). Independent risk factors associated with ESRD were as follows: proteinuria (hazard ratio [HR] per every 1 g/d increase. 1.16; 95% confidence interval [95% CI], 1.03 to 1.31; P=0.01), eGFR (HR per every 1 ml/min per 1.73 m(2) increase, 0.96; 95% CI, 0.94 to 0.97; P<0.001), T2 Oxford classification (tubular atrophy/interstitial fibrosis, >50%; HR, 4.42; 95% CI, 1.40 to 13.88; P=0.01), and C4d-positive staining (HR, 2.45; 95% CI, 1.30 to 4.64; P=0.01). C4d-positive staining is an independent risk factor for the development of ESRD in IgAN. This finding is consistent with the possibility that complement activation is involved in the pathogenesis of this disease.

Renal outcomes in IGa nephropathy: validation of the oxford classification in the Thai population

The Oxford classification of immunoglobulin A nephropathy (IgAN) was proposed to establish the risk of renal disease progression by specific pathologic features. This classification needs validation in different populations. A total of 126 patients with biopsy-proven IgAN at Ramathibodi Hospital between 2003 and 2012 with GFR above 30mL/min/1.73m² were enrolled in this retrospective study. The renal outcome was defined as the composite of 50% reduction in GFR and end state renal disease (ESRD). The Oxford classification was used to evaluate the pathologic lesions. The predictive values of clinicopathologic risk factors on renal survival were analyzed by univariate and multivariate models. The renal outcome occurred in 37 patients with median follow-up time of 49 months. Median renal survival was 121 months. In univariate time dependent analyses, only tubular atrophy/interstitial fibrosis was significantly associated with renal outcome. Other features such as crescentic lesions, mesangial hypercelluarity, endocapillary hypercelluarity, segmental glomerulosclerosis were not significant. In multivariate model, tubular atrophy/interstitial fibrosis (T1: HR 6.88, 95% CI 0.50–05.19; T2: HR 8.58, 95% CI 1.34–54.82) were independent risk factor for renal outcome. We confirmed that tubulointerstitial features of the Oxford classification of IgAN can predict renal survival in the Thai population.

Up-regulation of urinary markers predict outcome in IgA nephropathy but their predictive value is influenced by treatment with steroids and azathioprine

Steroids and immunosuppressants can delay progression of renal function in IgAN, but their possible effect in local cytokines has not been studied. Histology in 53 IgAN patients (M/F 35/18 age 40.5 years (17 - 65)) was evaluated using the Oxford classification system. IL-1β, -2, -4, -5, -6, -10, -12 and -17, INF-γ and MCP-1 were measured subsequently by multiplex cytokine assay in first morning urine samples taken at the day of renal biopsy. After a 6-month course with RAASinhibitors + fish oils (FO), 35/53 patients, Group A, responded and continued on the same treatment, while in 18/53 who did not respond, Group B, steroids + azathiopine were added. The presence of endocapillary proliferation had significant correlation with the urinary excretion of pro-inflammatory and pro-fibrotic cytokines (IL-1β, MCP-1, IL-17, INF-γ, IL-6 and IL-10). Serum creatinine at time of diagnosis had significant correlation with proteinuria (p = 0.02), urinary levels of IL-1β (p = 0.03), IL-2 (p = 0.01) and MCP-1 (p = 0.03). GFR was reduced from 65 ± 29 to 57 ± 34 ml/min, p = 0.005 in Group A and remained stable in Group B patients (GFR from 63 ± 24 to 61 ± 30 ml/min, p = NS). Most of the measured cytokines in the urine predicted deterioration of renal function in Group A, but the urinary excretion of IL-6 seemed to predict renal function outcome in both groups of patients. Several cytokines are excreted in the urine of patients with IgAN, and their levels predict the outcome of the disease. Steroids + aza may exert their beneficial effect through suppression of the production or activation of most cytokines.