Pathological predictors of renal outcomes in nephrotic idiopathic membranous nephropathy with decreased renal function

Chen, Yizhi; Li, Tang; Feng, Zhe; Cao, Xueying; Sun, Xuefeng; Liu, Moyan; Liu, Shuwen; Zhang, Xueguang; Li, Ping; Wei, Ri-bao; Qiu, Qiang; Cai, Guangyan; Chen, Xiangmei

doi:10.1007/s40620-014-0057-0

Cited by 28 publications

(31 citation statements)

References 31 publications

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Section: Discussionmentioning

confidence: 99%

“…The evaluation of FSGS as a predictor factor of renal function outcome has gained much interest but results remain conflicting, with some investigators supporting a pathogenic role of FSGS in declining renal function, providing FSGS and the severity of tubulointerstitial fibrosis as the only independent factors of disease outcome, [25][26][27][28] while others doubt that there is any correlation of FSGS with renal function outcome. 29,30 Based on the results from our study, FSGS and VH are important findings in the presence of NS, and additionally the presence of FSGS predicts a worse outcome in patients with preserved renal function at diagnosis.…”

Section: Discussionmentioning

confidence: 99%

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Histological grading in primary membranous nephropathy is essential for clinical management and predicts outcome of patients

et al. 2019

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AimsDiagnosis of primary membranous nephropathy (PMN) is mainly based on immunofluorescence/immunohistochemistry findings. However, assessment of specific features on optical microscopy can help to estimate the severity of the disease, guide treatment and predict the response. The aim of this study was to identify, classify and grade the precise histological findings in PMN to predict renal function outcome and guide treatment.Methods and resultsHistological parameters, including focal segmental sclerosis (FSGS), tubular atrophy (TA), interstitial fibrosis (IF) and vascular hyalinosis (VH), were re‐evaluated in 752 patients with PMN. Their predictive value was estimated separately, and also in a combination score (FSTIV) graded from 0 to 4. Finally, the impact of histology was assessed in the response to immunosuppressive treatment. Mean age of patients was 53.3 (15–85) years and most presented with nephrotic syndrome. FSGS was present in 32% and VH in 51% of the patients, while TA and IF were graded as stage ≥1 in 52% and 51.4%, respectively. The follow‐up period was 122.3 (112–376) months. FSGS, TA and IF and VH were associated with impaired renal function at diagnosis (P = 0.02, P < 0.0001, P = 0.001 and P = 0.02, respectively) and at the end of follow‐up (P = 0.004, P < 0.0001, P < 0.0001 and P = 0.04, respectively). In multiple regression and binary logistic analysis, the presence of FSGS and degree of TA were the most significant parameters predicting renal function outcome, defined either by eGFR (end), FSGS (r = 0.6, P < 0.0001) and TA (r = 0.6, P < 0.0001), or by the endpoint of >50% eGFR reduction, FSGS (P = 0.001) and TA (P = 0.02). Also, patients presented with FSGS, IF, VH and/or with FSTIV > 1 could benefit from immunosuppression, regardless of clinical presentation.ConclusionsThe presence and degree of four histological indices, FSGS, VH, TA and IF, assessed separately or in combination, and FSTIV score not only predict renal function outcome after long‐term follow‐up, but can also help in the choice of appropriate treatment. Decisions concerning immunosuppressive treatment can be guided by pathology regardless of clinical findings.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Histological grading in primary membranous nephropathy is essential for clinical management and predicts outcome of patients

et al. 2019

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“…It is also suggested by another Chinese study [ 28 ]. However, Chen et al found that the moderate or severe damage (> 25% of interstitium involved) was risk factor to ESKD [ 29 ]. The possible reason for this discrepancy may be that the patients in Chen’s study were restricted to those with nephrotic-range proteinuria (> 3.5 g/day) and CKD stages 2–4.…”

Section: Discussionmentioning

confidence: 99%

Clinical implications of pathological features of primary membranous nephropathy

Zhang¹,

Cui²,

Zhang³

et al. 2018

BMC Nephrol

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BackgroundThe clinical outcome varies considerably in primary membranous nephropathy (pMN). Risk factors for kidney prognosis include ageing, male gender, persistent heavy proteinuria, decreased eGFR at presentation, persistent elevation of anti-PLA2R antibodies, no remission, and so on. It was controversial whether the histopathological features of pMN could predict treatment response and kidney outcome.MethodsA retrospective study was conducted in 371 patients with biopsy-proven pMN. Pathological parameters included immunofluorescence staining, membranous Churg’s stages, sclerosis, crescent, focal segmental sclerosis lesion, chronic and acute tubulointerstitial injury. The fluorescence intensity was determined: 0, negative; 1, weak; 2, moderate; 3, strong; 4, glaring. Chronic tubulointerstitial injury was graded by the involved area: 0, 0–5%; 1, 6–25%; 2, 26–50%; 3, > 50%.ResultsWe found that patients with higher intensity of C3 staining, advanced membranous stage, and more severe chronic tubulointerstitial injury presented with higher positivity rate of anti-PLA2R antibodies, higher levels of urinary protein excretion and serum creatinine, and lower level of serum albumin. Univariate Cox regression analysis showed that severe (grade = 3) chronic tubulointerstitial injury was a risk factor to the kidney outcome of ESKD (HR = 61.02, 95%CI, 7.75–480.57, P < 0.001) and over 50% reduction of eGFR (HR = 4.43, 95%CI, 1.26–15.6, P = 0.021). Multivariate analysis demonstrated it as an independent risk factor to ESKD (HR = 25.77, 95% CI, 1.27–523.91, P = 0.035). None of the pathological parameters exerted any influence on treatment response (P > 0.05).ConclusionsWe found the prognostic role of chronic tubulointerstitial injury to the kidney outcome of pMN. This study highlighted the value of kidney biopsy under the widespread usage of anti-PLA2R antibodies for diagnosis and prognosis.Electronic supplementary materialThe online version of this article (10.1186/s12882-018-1011-5) contains supplementary material, which is available to authorized users.

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“…The severity of tubulointerstitial lesions is a key factor in determining the long-term kidney function of patients with glomerular disease. Notably, tubulointerstitial fibrosis and tubular atrophy are determinants of the progression of primary kidney disease [ 38 , 39 ]. Thus, it is assumed that patients with renal tubular C3 deposition exhibit a poorer prognosis compared with those without renal tubular C3 deposition.…”

Section: Discussionmentioning

confidence: 99%

Renal Tubular Complement 3 Deposition in Children with Primary Nephrotic Syndrome

Wang

Zhu

et al. 2018

BioMed Research International

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Background This study aimed to investigate the clinical significance of complement 3 (C3) deposition in renal tubules of children with primary nephrotic syndrome (PNS). Methods The clinical and pathological characteristics of PNS were retrospectively reviewed in 99 PNS pediatric patients, who were divided into the C3 deposition and the non-C3 deposition groups. Results A total of 39 patients (39.39%) had renal tubule C3 deposition. In the C3 deposition group, the ratios of urine N-acetylglucosaminidase/creatinine (UNAG/Cr), urine β2 microglobulin/creatinine (Uβ2MG/Cr), and urine transferrin/creatinine (UTRF/Cr) were significantly higher than those of the non-C3 deposition group. The patients of the C3 deposition group had lower serum total protein and albumin, higher cholesterol and D-dimer (DD), lower proportion of CD3+CD8+ cells, and higher proportion of CD19+CD23+ cells. The number of the patients with interstitial fibrosis, renal cell vacuolar degeneration, renal tubular immunoglobulin deposition, and severe tubulointerstitial injury in the C3 deposition group was higher than that of the non-C3 deposition group. The C3 deposition intensity was positively correlated with the number of recurrences. Conclusion PNS pediatric patients with C3 deposition in renal tubules have more severe disease condition, tubulointerstitial injury, and recurrence suggesting a worse long-term prognosis.

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Pathological predictors of renal outcomes in nephrotic idiopathic membranous nephropathy with decreased renal function

Abstract: Segmental sclerosis and tubulointerstitial injury predict renal outcomes independent of clinical data in nephrotic IMN patients with decreased renal function.

Cited by 28 publications

References 31 publications

Histological grading in primary membranous nephropathy is essential for clinical management and predicts outcome of patients

Histological grading in primary membranous nephropathy is essential for clinical management and predicts outcome of patients

Clinical implications of pathological features of primary membranous nephropathy

Renal Tubular Complement 3 Deposition in Children with Primary Nephrotic Syndrome

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