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

2019 ◽  
Author(s):  
Jhonny L Moreno ◽  
Lida M Rodas ◽  
Juliana Draibe ◽  
Xavier Fulladosa ◽  
Montserrat Gomá ◽  
...  

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.

2020 ◽  
Author(s):  
Ming Xia ◽  
Di Liu ◽  
Liang Peng ◽  
Yan Li ◽  
Haiyang Liu ◽  
...  

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.


2020 ◽  
Author(s):  
Bingxin Yu ◽  
Sufang Shi ◽  
Wanyin Hou ◽  
Lijun Liu ◽  
Jicheng Lv ◽  
...  

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.


2020 ◽  
Author(s):  
Ming Xia ◽  
Di Liu ◽  
Liang Peng ◽  
Yan Li ◽  
Haiyang Liu ◽  
...  

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 and 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 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.


2020 ◽  
Author(s):  
Ming Xia ◽  
Di Liu ◽  
Liang Peng ◽  
Yan Li ◽  
Haiyang Liu ◽  
...  

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.


2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Ming Xia ◽  
Di Liu ◽  
Liang Peng ◽  
Yan Li ◽  
Haiyang Liu ◽  
...  

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 (< 11.15 s) or APTT (< 29.65 s) 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 (< 11.15 s) or APTT (< 29.65 s). 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.


2018 ◽  
Vol 34 (10) ◽  
pp. 1681-1690 ◽  
Author(s):  
Shubha S Bellur ◽  
Ian S D Roberts ◽  
Stéphan Troyanov ◽  
Virginie Royal ◽  
Rosanna Coppo ◽  
...  

Abstract Background The VALidation of IGA (VALIGA) study investigated the utility of the Oxford Classification of immunoglobulin A nephropathy (IgAN) in 1147 patients from 13 European countries. Methods. Biopsies were scored by local pathologists followed by central review in Oxford. We had two distinct objectives: to assess how closely pathology findings were associated with the decision to give corticosteroid/immunosuppressive (CS/IS) treatments, and to determine the impact of differences in MEST-C scoring between central and local pathologists on the clinical value of the Oxford Classification. We tested for each lesion the associations between the type of agreement (local and central pathologists scoring absent, local present and central absent, local absent and central present, both scoring present) with the initial clinical assessment, as well as long-term outcomes in those patients who did not receive CS/IS. Results All glomerular lesions (M, E, C and S) assessed by local pathologists were independently associated with the decision to administer CS/IS therapy, while the severity of tubulointerstitial lesions was not. Reproducibility between local and central pathologists was moderate for S (segmental sclerosis) and T (tubular atrophy/interstitial fibrosis), and poor for M (mesangial hypercellularity), E (endocapillary hypercellularity) and C (crescents). Local pathologists found statistically more of each lesion, except for the S lesion, which was more frequent with central review. Disagreements were more likely to occur when the proportion of glomeruli affected was low. The M lesion, assessed by central pathologists, correlated better with the severity of the disease at presentation and discriminated better with outcomes. In contrast, the E lesion, evaluated by local pathologists, correlated better with the clinical presentation and outcomes when compared with central review. Both C and S lesions, when discordant between local and central pathologists, had a clinical phenotype intermediate to double absent lesions (milder disease) and double present (more severe). Conclusion We conclude that differences in the scoring of MEST-C criteria between local pathologists and a central reviewer have a significant impact on the prognostic value of the Oxford Classification. Since the decision to offer immunosuppressive therapy in this cohort was intimately associated with the MEST-C score, this study indicates a need for a more detailed guidance for pathologists in the scoring of IgAN biopsies.


2018 ◽  
Vol 48 (2) ◽  
pp. 127-136 ◽  
Author(s):  
Bin Zhu ◽  
Dong-rong Yu ◽  
Ji-cheng Lv ◽  
Yi Lin ◽  
Qiang Li ◽  
...  

Background: The role of serum uric acid (SUA) level in the progression of Immunoglobulin A nephropathy (IgAN) remains controversial. Methods: In a cohort of 1,965 cases with biopsy-proven IgAN, we examined the associations of SUA concentration with the primary outcome of a composite of all-cause mortality or kidney failure (defined as a reduction of estimated glomerular filtration rate [eGFR] by 40% from baseline, requirements for dialysis and transplantation), or the outcome of kidney failure alone, assessed using Cox and logistic regression models, respectively, with adjustment for confounders. Results: At baseline, the mean age was 33.37 ± 11.07 years, eGFR was 101.30 ± 30.49 mL/min/1.73 m2, and mean uric acid level was 5.32 ± 1.76 mg/dL. During a median of 7-year follow-up, 317 cases reached the composite outcome of all-cause mortality (5 deaths) or kidney failure (36 cases of dialysis, 5 cases of renal transplantation, and 271 cases with reduction of eGFR by 40% from baseline). After adjustment for demographic and IgAN specific covariates and treatments, a higher quartile of uric acid was linearly associated with an increased risk of the primary outcome (highest versus lowest quartile, hazard ratio [HR] 2.39; 95% CI 1.52–3.75) and kidney failure (highest versus lowest quartile, HR 2.55; 95% CI 1.62–4.01) in the Cox proportional hazards regression models. In the continuous analysis, a 1 mg/dL greater uric acid level was associated with 16% increased risk of primary outcome (HR 1.16, 95% CI 1.07–1.25) and 17% increased risk of kidney failure (HR 1.17, 95% CI 1.08–1.27), respectively, in the fully adjusted model. The multivariate ­logistic regression analyses for the sensitive analyses drew consistent results. In the subgroup analyses, significant interactions were detected that patients with mean arterial pressure (MAP) < 90 mm Hg or mesangial hypercellularity had a higher association of SUA with the incidence of the primary outcome than those with MAP ≥90 mm Hg or those without mesangial hypercellularity respectively. Hyperuricemia was not significantly associated with the risk of developing the primary outcome in elder patients (≥32 years old), patients with eGFR < 90 mL/min or with tubular atrophy/interstitial fibrosis. Conclusions: SUA level may be positively associated with the progression of IgAN. It was noticeable that the association of hyperuricemia with IgAN progression was less significant in patients with elder age, lower eGFR, or tubular atrophy/interstitial fibrosis, which may be due to some more confounders in association with the IgA progression in these patients. Future prospective studies are warranted to confirm these findings and to investigate the underlying mechanisms.


2019 ◽  
Author(s):  
Heyan Wu ◽  
Zhengkun Xia ◽  
Chunlin Gao ◽  
Pei Zhang ◽  
Xiao Yang ◽  
...  

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.


2018 ◽  
Vol 35 (6) ◽  
pp. 1002-1009 ◽  
Author(s):  
Rosanna Coppo ◽  
Graziella D'Arrigo ◽  
Giovanni Tripepi ◽  
Maria Luisa Russo ◽  
Ian S D Roberts ◽  
...  

Abstract Background It is unknown whether renal pathology lesions in immunoglobulin A nephropathy (IgAN) correlate with renal outcomes over decades of follow-up. Methods In 1130 patients of the original Validation Study of the Oxford Classification for IgA Nephropathy (VALIGA) cohort, we studied the relationship between the MEST score (mesangial hypercellularity, M; endocapillary hypercellularity, E; segmental glomerulosclerosis, S; tubular atrophy/interstitial fibrosis, T), crescents (C) and other histological lesions with both a combined renal endpoint [50% estimated glomerular filtration rate (eGFR) loss or kidney failure] and the rate of eGFR decline over a follow-up period extending to 35 years [median 7 years (interquartile range 4.1–10.8)]. Results In this extended analysis, M1, S1 and T1–T2 lesions as well as the whole MEST score were independently related with the combined endpoint (P &lt; 0.01), and there was no effect modification by age for these associations, suggesting that they may be valid in children and in adults as well. Only T lesions were associated with the rate of eGFR loss in the whole cohort, whereas C showed this association only in patients not treated with immunosuppression. In separate prognostic analyses, the whole set of pathology lesions provided a gain in discrimination power over the clinical variables alone, which was similar at 5 years (+2.0%) and for the whole follow-up (+1.8%). A similar benefit was observed for risk reclassification analyses (+2.7% and +2.4%). Conclusion Long-term follow-up analyses of the VALIGA cohort showed that the independent relationship between kidney biopsy findings and the risk of progression towards kidney failure in IgAN remains unchanged across all age groups and decades after the renal biopsy.


Author(s):  
Anna Jana Saulīte ◽  
Anna Popova ◽  
Renārs Erts ◽  
Kārlis Rācenis ◽  
Linda Kučāne ◽  
...  

Abstract The aim of the study was to determine kidney survival and validate the novel international immunoglobulin A nephropathy (IgAN) prediction tool (PT) in the Latvian population. Adults with morphologically confirmed IgAN were included. Kidney survival was analysed with the Kaplan–Meier method. PT-assigned risk was compared with calculated risk by the Cox regression model. The Kaplan–Meier analysis included 95 patients. The five-year kidney survival Q3 was 24 months. Women had longer median kidney-survival time (> 60 months) than men (58 months). Median kidney survival in participants with MEST T0 was longer than 60 months; T1 and T2 were 40 and 18 months, respectively. Median kidney survival in participants with diastolic blood pressure (DBP) < 99 mmHg was longer than 60 months, whereas in patients with DBP 100–109 and 110 mmHg, it was 40 and 24 months, respectively. Cox regression analysis included 68 patients. A moderate degree of correlation was found between predicted and observed five-year risk (p = 0.001). Gender, tubular atrophy/interstitial fibrosis, DBP are significant factors affecting kidney survival. Since there was statistically significant correlation and reliability between PT and follow-up analysis data, we conclude that PT could be applied for use in the Latvian population.


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