P0368THE ADDED IMPACT OF CRESCENTS ON DEVELOPMENT OF END-STAGE KIDNEY DISEASE IN COMBINATION WITH OTHER PATHOLOGICAL FEATURES OF OXFORD CLASSIFICATION IN PATIENTS WITH IGA NEPHROPATHY

Abstract Background and Aims Oxford classification of IgA nephropathy (IgAN) consists of the presence of four 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 renal outcome has been evaluated in previous studies. More recently crescents (C) were added to Oxford classification but the additive effect of the crescents on prediction of renal outcome is less well studied. The aim of the study was to assess the added impact of crescents, as an independent variable, on development of end stage kidney disease (ESKD) in combination with other pathological features of Oxford classification, in patients with IgAN. Method One- hundred fifteen patients with IgAN (76% male, mean age: 37±13 years, mean serum creatinine: 4.0±4.3 mg/dl and mean proteinuria: 3.4±2.5 g/24 hours) were followed for 43±29 months. MEST score was defined according to Oxford classification (M0/M1, E0/E1, S0/S1). To increase the power of the study, T was defined as T0<25% and T1≥ 25%. Crescents were defined as C0: absence and C1: at least one crescents in biopsy. Additionally in sensitivity analysis, the risk of ESKD was estimated at different cut-off levels of at least 10%, 20% and 30% crescents. Furthermore the additive effect of the presence of crescents on the other Oxford classification score was studied. Association between Oxford Classification score and risk of ESKD was examined by time-dependent Cox model to estimate hazard ratio, through univariate and multivariate analyses, adjusted for demographics, laboratory and pathological findings. Kaplan–Meier and the log-rank tests were used to estimate kidney survival. Results During follow-up 40 patients (35%) developed ESKD (dialysis or kidney transplantation). Forty- six patients (40%) had at least one crescent and among them 25 (46%) developed ESKD. In sub- analysis in 11 patients with C≥30%, 7 (66%) developed ESKD. Among 57 patients with T1, 34 (60%) developed ESKD. Twenty- seven patients had both T1 and C1 and among them 20 (74%) developed ESKD. In adjusted model, among patients with crescents, only C≥30% (HR: 3.15, 95% CI 1.15-11.00,P=0.027) and the presence of T1+ C1 (HR: 7.18, 95% CI 1.90-27.10,P=0.004) were associated with increased risk of ESKD and the combinations of M1+C1, E1+C1 or S1+C1 were not significantly associated with increased risk of ESKD (P=0.067, P=0.450, P=0.035, respectively). The median kidney survival was 78.0 months (95% CI, 70.5-85.6 months) with T0+C0 and 32.3 months (95% CI, 19.3-45.3 months) with T1+C1. Conclusion In this study based on Oxford classification, tubular atrophy and interstitial fibrosis≥25%, and presence of crescents≥ 30%, were independently associated with increased risk of ESKD. This risk was strongly increased in combined presence of at least one crescent and T1≥25% and 74% of such patients developed ESKD within a mean interval of 27 months.

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Evaluation of the Oxford classification in immunoglobulin A vasculitis with nephritis: a cohort study and meta-analysis

Clinical Kidney Journal ◽

10.1093/ckj/sfaa129 ◽

2020 ◽

Author(s):

Bingxin Yu ◽

Sufang Shi ◽

Wanyin Hou ◽

Lijun Liu ◽

Jicheng Lv ◽

...

Keyword(s):

Cohort Study ◽

Interstitial Fibrosis ◽

Meta Analysis ◽

Immunoglobulin A ◽

Renal Outcome ◽

Oxford Classification ◽

Tubular Atrophy ◽

The Oxford Classification ◽

Stage Renal Disease ◽

End Stage

Abstract Background Similarities in clinicopathological presentations in immunoglobulin A (IgA) nephropathy and IgA vasculitis with nephritis (IgAVN) raise the question of the utility of the Oxford classification in the latter. The aim of this study was to evaluate the Oxford classification in IgAVN. Methods We conducted a retrospective cohort study and meta-analysis following systematic searching of the MEDLINE and Excerpta Medica Database (EMBASE) databases between January 2009 and September 2019. We modeled the association of 30 and 50% decline in estimated glomerular filtration rate or end-stage renal disease with pathologic lesions of the Oxford classification including mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental glomerulosclerosis (S), interstitial fibrosis/tubular atrophy (T) and crescents (C). Results were pooled using random-effects meta-analysis. Results The cohort study included 132 patients, and only T lesion was an independently risk factor in IgAVN. The meta-analysis yielded six retrospective studies with 721 patients and 139 endpoints. In multivariate model, T lesion was significantly associated with renal outcome (hazard ratio = 2.45, P = 0.007). M and C lesions could not predict renal outcome without evidence of heterogeneity. E and S lesions could not predict renal outcome with evidence of heterogeneity (I2 = 66.6%; P = 0.01, and I2 = 65.8%; P = 0.03, respectively). Subgroup analysis showed that the possible reasons to the heterogeneity were from usage of immunosuppressant, sample size and follow-up time. Conclusions The study suggests that the Oxford classification could not be fully validated in IgAVN. Higher portion of immunosuppressant especially before renal biopsy might be the main confounder for the predictive value of Oxford classification in IgAVN.

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P0440EPIDEMIOLOGICAL AND CLINICAL CHARACTERSTICS OF IGA NEPHROPATHY PATIENTS IN TURKEY: TSN-GOLD WORKING GROUP

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0440 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Necmi Eren ◽

Meltem Gursu ◽

Egemen Cebeci ◽

Aydin Turkmen ◽

Hasan Haci Yeter ◽

...

Keyword(s):

Iga Nephropathy ◽

Clinical Data ◽

Working Group ◽

Interstitial Fibrosis ◽

Renal Outcome ◽

Pathological Features ◽

Oxford Classification ◽

Tubular Atrophy ◽

Glomerular Diseases ◽

Lower Egfr

Abstract Background and Aims According to the data of the Turkish Society of Nephrology-Glomerular Diseases Working Group (TSN-GOLD Working Group), IgA nephropathy is the most common primary glomerular disease in Turkey. The purpose of this study was to investigate the epidemiological and clinical data of IgA nephropathy patients in Turkey. Method 4399 patients with primary glomerular diseases from 47 centers who were followed up between May 2009 and May 2019 were included in the study conducted by TSN-GOLD Working Group. 524 patients were excluded due to lack of pathological data. Among the remaining patients, demographic, clinical and laboratory data of 994 patients with IgA nephropathy were analyzed. Results The median age of the patients was 37 (28-47) years, and 37.3% of them were female. The laboratory and clinical data at the time of diagnosis is presented in Figure-1, and biopsy indications are described in Figure-2. The median number of glomeruli was 16 (IQR: 3.5-4.3), sclerotic glomeruli was 2 (IQR: 1-5), and segmental sclerotic glomeruli was 1 (IQR: 1-2). Exudative changes, subendothelial and subepithelial deposition were present in 566 patients (56.9%), 46 patients (4.6%) and in 38 patients (3.8%), respectively. 662 (66.1%) and 611 of the patients (61.4%) had tubular atrophy and interstitial fibrosis in varying degrees, respectively. 672 (%67.6) and 416 patients (%41.9) had interstitial inflammation and vascular changes, respectively. In immunofluorescence staining, 18%, 30.1%, 4.4%, 68% of the patients had IgG, IgM, C1q and C3 positivity, respectively. Crescentic glomeruli were detected in 227 patients (3.3 ± 3.1 glomeruli). Patients with crescentic glomeruli had significantly higher proteinuria and lower eGFR than the patients without [2203 mg/day (15-26078) vs 1807 mg/day (15-29112); p=0.001; 55.3 ml/min/1.73 m2 (3.72-141.9) vs 72 ml/min/1.73 m2 (3.84-150.81); p<0.001, respectively]. Oxford classification was applied to 544 patients. Endocapillary hypercellularity (E1), mesengial hypercellularity (M1), tubular atrophy and interstitial fibrosis (T1 and T2), segmental sclerosis (S1) were present in 126 (13%), 425 (42.8%), 306 (30.8%) and 325 patients (%32.7), respectively. Proteinuria levels were higher in patients with endocapillary hypertrophy, mesengial hypercellularity, tubular atrophy-interstitial fibrosis and segmental sclerosis. eGFR levels were lower in patients with endocapillary hypertrophy, tubular atrophy-interstitial fibrosis and segmental sclerosis (Figure-3). Conclusion In this study we found that, the most common presentation of IgA nephropathy patients in our country was asymptomatic urinary abnormalities followed by nephritic and nephrotic syndrome. Higher proteinuria and lower eGFR values in patients with crescentic glomeruli, support the adoption of crescentic lesions in the new Oxford classification (MEST-C) to predict more precise outcome of IgA nephropathy patients. The high number of patients to whom the Oxford classification was applied provided us with the opportunity to examine the clinical reflections of pathological features. Evaluation of the follow-up data of the patients will give us the possibility to reveal the effect of initial clinical and pathological features on clinical findings and renal outcome.

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

10.21203/rs.2.22607/v2 ◽

2020 ◽

Author(s):

Elodie Miquelestorena-Standley ◽

Charlotte Jaulerry ◽

Marie-Christine Machet ◽

Nolwenn Rabot ◽

Christelle Barbet ◽

...

Keyword(s):

Interstitial Fibrosis ◽

Outcome Data ◽

Renal Outcome ◽

Tubular Atrophy ◽

Short Delay ◽

Adult Men ◽

Staphylococcus Infections ◽

Endocapillary Proliferative Glomerulonephritis ◽

Stage Renal Disease ◽

End Stage

Abstract 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.

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

10.21203/rs.2.22607/v1 ◽

2020 ◽

Author(s):

Elodie Miquelestorena-Standley ◽

Charlotte Jaulerry ◽

Marie-Christine Machet ◽

Nolwenn Rabot ◽

Christelle Barbet ◽

...

Keyword(s):

Interstitial Fibrosis ◽

Outcome Data ◽

Renal Outcome ◽

Chi Square ◽

Tubular Atrophy ◽

Adult Men ◽

Chi Square Test ◽

Endocapillary Proliferative Glomerulonephritis ◽

Stage Renal Disease ◽

End Stage

Abstract 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.

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The Correlation Analysis between the Oxford Classification of Chinese IgA Nephropathy Children and Renal Outcome -A retrospective cohort study

10.21203/rs.2.13992/v1 ◽

2019 ◽

Author(s):

Heyan Wu ◽

Zhengkun Xia ◽

Chunlin Gao ◽

Pei Zhang ◽

Xiao Yang ◽

...

Keyword(s):

Risk Factors ◽

Iga Nephropathy ◽

Interstitial Fibrosis ◽

Cohort Analysis ◽

Immunosuppressive Agents ◽

Renal Outcome ◽

Oxford Classification ◽

Tubular Atrophy ◽

Independent Risk Factors

Abstract Background The 2016 Oxford Classification's MEST-C scoring system predicts outcomes in adults with IgA nephropathy, but it lacks large cohort validation in children with IgAN in China. We would like to verify that the MEST-C score can be used to predict the renal outcome of children with IgAN.Methods A retrospective cohort analysis of data from 1243 Chinese children with IgAN who underwent renal biopsy in Jinling Hospital from 2000 to 2017 was performed and investigated with glomerular filtration rate (eGFR),24h urine proteinuria(24h-UP)and blood pressure(BP) at biopsy and during follow-up.The renal pathology was based on Oxford Classification of IgAN.Results We confirm that BP was significantly correlated with mesangial hypercellullarity(M), endocapillary hypercellularity(E), tubular atrophy/ interstitial fibrosis(T) and crescents (C) .There was a significant correlation between eGFR and segmental glomerulosclerosis(S), T and C .24h-UP and all pathological indexes were significantly correlated. S and T were shown to be independent risk factors associated with renal outcomes in our group. Kaplan-Meier revealed that M [log-rank, chi-squared(χ2)=14.679, P=0.000 ], S(χ2=31.508,P=0.000),T (χ2=78.893, P=0.000),C(χ2=16.603, P=0.000) were associated with renal outcome.In univariate analyses, M(HR 2.167, 95% CI, 1.445~3.251, P = 0.000),S(HR 3.081, 95% CI, 2.038~4.658, P = 0.000), T(HR 7.911, 95% CI, 4.670~13.400,P = 0.000) and C(HR3.346, 95% CI, 1.818~6.156,P = 0.000) lesions were significant predictors of renal outcome. In a multivariate analysis, only S(HR 2.742, 95% CI, 1.805~4.164,P = 0.000) and T(HR 6.633, 95% CI, 3.897~11.289,P = 0.000)were shown to be independent risk factors .Conclusions We found that S and T lesions were valid in predicting a poor outcome in our group.E, S, T and C lesion were important basis for doctors to choose glucocorticoids and immunosuppressive agents in the treatment of IgAN, while T and C lesion were often the basis for doctors to use RAS blockers cautiously.

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The Correlation Analysis between the Oxford Classification of Chinese IgA Nephropathy Children and Renal Outcome -A retrospective cohort study

10.21203/rs.2.13992/v3 ◽

2020 ◽

Author(s):

Heyan Wu ◽

Zhengkun Xia ◽

Chunlin Gao ◽

Pei Zhang ◽

Xiao Yang ◽

...

Keyword(s):

Cohort Study ◽

Iga Nephropathy ◽

Retrospective Cohort Study ◽

Cortical Area ◽

Retrospective Cohort ◽

Interstitial Fibrosis ◽

Renal Outcome ◽

Oxford Classification ◽

Tubular Atrophy ◽

The Oxford Classification

Abstract Background: The 2016 Oxford Classification's MEST-C scoring system predicts outcomes in adults with IgA nephropathy (IgAN), but it lacks large cohort validation in children with IgAN in China. We sought to verify whether the Oxford classification could be used to predict the renal outcome of children with IgAN. Methods : A total of 1243 Chinese children with IgAN who underwent renal biopsy in Jinling Hospital were enrolled from January 1, 2000, to December 31, 2017, in this retrospective cohort study. The primary endpoint of the study was a composite of either ≥50% reduction in estimated glomerular filtration rate (eGFR) or end-stage renal disease (ESRD). We probed into the relationship between the Oxford classification and renal outcome. Results : There were 29% of children with mesangial proliferation(M1), 35% with endocapillary proliferation (E1), 37% with segmental sclerosis/adhesion lesion (S1), 23% with moderate tubular atrophy/interstitial fibrosis (T1 25–50% of cortical area involved), 4.3% with severe tubular atrophy/interstitial fibrosis (T2 >50% of cortical area involved), 44% with crescent in< 25% of glomeruli(C1), and 4.6% with crescent in>25% of glomeruli (C2).During a median follow-up duration of 7.2 (4.6–11.7) years, 171 children (14%) developed ESRD or 50% decline in eGFR. In the multivariate COX regression model, only segmental sclerosis/adhesion (HR2.7,95%CI 1.8～4.2, P ＜0.001) and tubular atrophy/interstitial fibrosis (HR6.6,95%CI 3.9～11.3, P ＜0.001) were confirmed to be independent risk factors of poor renal outcome in the whole cohort, whereas crescent showed significant association with prognosis only in children received no immunosuppressive treatment.Conclusions: This study revealed that segmental sclerosis/adhesion and tubular atrophy/interstitial fibrosis were independently associated with poor renal outcome in Chinese children with IgA nephropathy.

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Extracapillary proliferation scoring correlates with renal outcome and contributes to stratification in adult patients with immunoglobulin A nephropathy

Clinical Kidney Journal ◽

10.1093/ckj/sfz133 ◽

2019 ◽

Author(s):

Jhonny L Moreno ◽

Lida M Rodas ◽

Juliana Draibe ◽

Xavier Fulladosa ◽

Montserrat Gomá ◽

...

Keyword(s):

Renal Function ◽

Interstitial Fibrosis ◽

Severe Disease ◽

Immunoglobulin A ◽

Renal Outcome ◽

Immunoglobulin A Nephropathy ◽

Renal Survival ◽

Oxford Classification ◽

Tubular Atrophy ◽

Renal Biopsies

Abstract Background The revised Oxford classification of diagnostic renal biopsies has been proposed to aid in the prediction of renal outcome. We aimed to validate the histological crescents and interstitial fibrosis and tubular atrophy (IFTA) subgrouping, and to investigate the additional value of the proportion of crescents (CatPE) in the prediction of renal outcome. Methods Data were retrospectively collected over 10 years, from the time of diagnosis, by systematic review of medical records from 90 patients with renal biopsies recruited to cohorts from two hospitals in Spain. Patients were classified into three groups for the analysis: CatPE >25% (C2), CatPE <25% (C1) and without this type of lesion (C0). The end point was renal survival defined by either >50% reduction in glomerular filtrate rate or end-stage renal disease. Results Renal survival at 5 years was 90% in group C0, 81% in group C1 and 31% in group C2 (P = 0.013). The presence of >25% crescents in the sample was associated with more severe disease when compared with <25%, as demonstrated by more interstitial fibrotic change and by lower estimated glomerular filtration rate at diagnosis, as well as worse renal function at 2 and 5 years. At the time of diagnosis and at 24 months, the group with IFTA >50% had poorer renal function compared with the other groups. Conclusions We have confirmed the predictive value for renal survival of the revised Oxford classification in a two-centre study. We found worse renal outcome in patients with severe tubulointerstitial fibrosis and atrophy. Patients with extracapillary lesions >25% and IFTA >50% had a worse renal prognosis due to more severe kidney injury. These results contribute to patient stratification in immunoglobulin A nephropathy for therapeutic, epidemiological and basic research.

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Recent advances in understanding of chronic kidney disease

F1000Research ◽

10.12688/f1000research.6970.1 ◽

2015 ◽

Vol 4 ◽

pp. 1212 ◽

Cited By ~ 9

Author(s):

Junna Yamaguchi ◽

Tetsuhiro Tanaka ◽

Masaomi Nangaku

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Pathological Features ◽

Tubular Epithelial Cells ◽

Epigenetic Factors ◽

End Stage Kidney Disease ◽

Tubular Atrophy ◽

Recent Advances ◽

End Stage ◽

Reduced Kidney Function

Chronic kidney disease (CKD) is defined as any condition that causes reduced kidney function over a period of time. Fibrosis, tubular atrophy and interstitial inflammation are the hallmark of pathological features in CKD. Regardless of initial insult, CKD has some common pathways leading CKD to end-stage kidney disease, including hypoxia in the tubulointerstitium and proteinuria. Recent advances in genome editing technologies and stem cell research give great insights to understand the pathogenesis of CKD, including identifications of the origins of renal myofibroblasts and tubular epithelial cells upon injury. Environmental factors such as hypoxia, oxidative stress, and epigenetic factors in relation to CKD are also discussed.

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Cardiopulmonary exercise testing (CPET) in patients with end-stage kidney disease (ESKD): principles, methodology and clinical applications of the optimal tool for exercise tolerance evaluation

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab150 ◽

2021 ◽

Author(s):

Eva Pella ◽

Afroditi Boutou ◽

Aristi Boulmpou ◽

Christodoulos E Papadopoulos ◽

Aikaterini Papagianni ◽

...

Keyword(s):

Kidney Disease ◽

Exercise Testing ◽

Cardiopulmonary Exercise Testing ◽

Exercise Intolerance ◽

End Stage Kidney Disease ◽

Exercise Limitation ◽

Cardiopulmonary Exercise ◽

Functional Reserves ◽

Increased Risk ◽

End Stage

Abstract Chronic kidney disease (CKD), especially end-stage kidney disease (ESKD), is associated with increased risk for cardiovascular events and all-cause mortality. Exercise intolerance as well as reduced cardiovascular reserve are extremely common in patients with CKD. Cardiopulmonary exercise testing (CPET) is a non-invasive, dynamic technique that provides an integrative evaluation of cardiovascular, pulmonary, neuropsychological and metabolic function during maximal or submaximal exercise, allowing the evaluation of functional reserves of these systems. This assessment is based on the principle that system failure typically occurs when the system is under stress and, thus, CPET is currently considered to be the gold-standard for identifying exercise limitation and differentiating its causes. It has been widely used in several medical fields for risk stratification, clinical evaluation and other applications but its use in everyday practice for CKD patients is scarce. This article describes the basic principles and methodology of CPET and provides an overview of important studies that utilized CPET in patients with ESKD, in an effort to increase awareness of CPET capabilities among practicing nephrologists.

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Coagulation parameters are associated with the prognosis of immunoglobulin A nephropathy: a retrospective study

10.21203/rs.3.rs-34312/v2 ◽

2020 ◽

Author(s):

Ming Xia ◽

Di Liu ◽

Liang Peng ◽

Yan Li ◽

Haiyang Liu ◽

...

Keyword(s):

Retrospective Study ◽

Interstitial Fibrosis ◽

Immunoglobulin A ◽

Coagulation System ◽

Renal Outcome ◽

Immunoglobulin A Nephropathy ◽

Tubular Atrophy ◽

Coagulation Parameters ◽

T Score ◽

Stage Renal Disease

Abstract Background: Interstitial fibrosis/tubular atrophy (T) score is a known determinant of the progression of immunoglobulin A nephropathy (IgAN). Strong evidence indicates that the components of the coagulation system closely linked with fibrotic events have been highlighted in the kidney. However, whether the coagulation system can affect the renal outcome of IgAN remains unclear. Herein, we investigated the association of coagulation parameters and pathological phenotype of IgAN and their combined effects on the deterioration of renal function. Methods: This retrospective study included N=291 patients with biopsy-proven IgAN from May 2009 to April 2013 in the Second Xiangya Hospital. Clinical data, pathological features were collected, and the associations of coagulation parameters at biopsy, T score, and renal outcome were evaluated. T score indicated the degree of tubular atrophy or interstitial fibrosis. The renal outcome was defined as an end-stage renal disease (ESRD) or an irreversible 50% estimated glomerular filtration rate (eGFR) reduction. Results: Shorter prothrombin time (PT) and the activated partial thromboplastin time (APTT) were significantly associated with T (both p<0.001). PT (<11.15s) or APTT (<29.65s) had worse cumulative survival rate (p=0.008, p=0.027 respectively) and were significantly but not independently associated with a higher risk of renal outcome (p=0.012, p=0.032 respectively). In the combined analyses of PT, APTT, and T lesions, the odd ratios for the outcome were significantly higher in the presence of T with PT (<11.15s) or APTT (<29.65s). Conclusion: Shorter PT and APTT are associated with an increased incidence of the T lesion and are additional factors that portend a poorer prognosis in IgAN. Monitoring coagulation function might be important when assessing the risk of progression. Additional studies exploring the molecular mechanism between coagulation and IgAN pathology are needed.

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