Dataset Information

Key pathological features characterize minimal change disease-like IgA nephropathy.

ABSTRACT:

Aims

A subset of IgA nephropathy (IgAN) patients exhibiting minimal change disease (MCD) like features present with nephrotic-range proteinuria and warrants immunosuppressive therapy (IST). However, the diagnosis of MCD-like IgAN varied by reports. We aimed to identify the key pathological features of MCD-like IgAN.

Methods

In this cohort, 228 patients had biopsy-proven IgAN from 2009 to 2021, of which 44 without segmental sclerosis were enrolled. Patients were classified into segmental (< 50% glomerular capillary loop involvement) or global (> 50%) foot process effacement (FPE) groups. We further stratified them according to the usage of immunosuppressant therapy after biopsy. Clinical manifestations, treatment response, and renal outcome were compared.

Results

26 cases (59.1%) were classified as segmental FPE group and 18 cases (40.9%) as global FPE group. The global FPE group had more severe proteinuria (11.48 [2.60, 15.29] vs. 0.97 [0.14, 1.67] g/g, p = 0.001) and had a higher proportion of complete remission (81.8% vs. 20%, p = 0.018). In the global FPE group, patients without IST experienced more rapid downward eGFR change than the IST-treated population (-0.38 [-1.24, 0.06] vs. 1.26 [-0.17, 3.20]mL/min/1.73 m2/month, p = 0.004).

Conclusions

The absence of segmental sclerosis and the presence of global FPE are valuable pathological features that assist in identifying MCD-like IgAN.

SUBMITTER: Wang TY

PROVIDER: S-EPMC10358932 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Key pathological features characterize minimal change disease-like IgA nephropathy.

Wang Tsung-Yueh TY Chang Fu-Pang FP Yang An-Hang AH Ka Shuk-Man SM Chen Ann A Hsieh Jyh-Tong JT Chen Fan-Yu FY Lee Tsung-Lun TL Tseng Po-Yu PY Tsai Ming-Tsun MT Li Szu-Yuan SY Yang Chih-Yu CY Chen Jinn-Yang JY Lin Chih-Ching CC Tarng Der-Cherng DC

PloS one 20230720 7

<h4>Aims</h4>A subset of IgA nephropathy (IgAN) patients exhibiting minimal change disease (MCD) like features present with nephrotic-range proteinuria and warrants immunosuppressive therapy (IST). However, the diagnosis of MCD-like IgAN varied by reports. We aimed to identify the key pathological features of MCD-like IgAN.<h4>Methods</h4>In this cohort, 228 patients had biopsy-proven IgAN from 2009 to 2021, of which 44 without segmental sclerosis were enrolled. Patients were classified into seg ...[more]

PMID: 37471324

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Project description:Introduction: Minimal change disease (MCD) is a major cause of nephrotic syndrome. With a substantial number of patients requiring long-term immunosuppression leading to significant morbidity, the study aim was to determine MCD glomerular transcriptome to serve as a basis for biomarker discovery and novel drug target identification. Animal work showed podocyte injury induced by IL-7/IL-7R signaling (Zhai S, BBRC, 2018). Methods: Renal biopsies from adult patients representing the following groups were selected from the Norwegian Kidney Biopsy Registry: MCD (n=14), as well as normal tissue (n=8) and primary membranous nephropathy (MN; n=12) as the two reference groups. RNA for 75 base-pair paired-end RNASeq was obtained by dissecting glomeruli via laser capture microdissection (LCM) from FFPE cross-sections. Systematic delineation of condition-specific alteration in transcriptional landscapes was achieved by combining pathway-centered analyses with methodologies derived from network science and integrating multiple bioinformatics resources. Results: Compared to normal glomeruli, glomeuli from MCD displayed an inflammatory signature that appeared to be predominantly governed by the IL1 and IL7 systems. While enrichment of IL1 production and secretion was a shared feature of MCD and MN compared to normal tissue, responses involving IL7 pathway activation were unique to MCD. Indeed, IL7R expressed by glomeruli was the most up-regulated gene of to the interleukin-family in MCD vs normal controls. IL7 pathway activation was paralleled by significant enrichment in adaptive immune system processes and transcriptional regulation and depletion in pathways related to energy metabolism and transcription. Downregulation of these organ function-related themes again occurred predominately in MDC and were significantly less pronounced in MN. Conclusion: Our results demonstrate that archival FFPE-biopsies can be used to generate glomeruli-specific gene expression profiles suitable for systematic delineation of kidney-associated diseases. Here the latter provides a data-driven rationale to experimentally address these MCD-specific features as biomarkers and as novel drug targets. In this context inhibiting activation of the IL7 pathway may be particularly promising.

Project description:Background and objectivesPoly-IgA immune complex formation and glomerular deposition play a key role in IgA nephropathy. Our study sought to develop a new methodology for one-step serologic detection of poly-IgA levels.Design, setting, participants, & measurementsA novel ELISA method using recombinant CD89 as a "capturing" probe was established for detecting poly-IgA immune complex in plasma. We applied semiquantitative measurements of these poly-IgA indices in patients recruited at Peking University First Hospital who had IgA nephropathy or other kidney disease types, as compared with healthy controls. The longitudinal trend of the poly-IgA index and the association with pathologic parameters and treatment responses were evaluated. Finally, we analyzed the molecular composition of poly-IgA complexes in patients by mass spectrometry.ResultsRecombinant CD89-mounted ELISA plates specifically captured plasma poly-IgA. The levels of poly-IgA immune complex (26.7 [interquartile range (IQR) 17.1-42.6] U/ml) in IgA nephropathy were significantly higher than those in healthy controls (15.5 [IQR 10.7-20.0] U/ml; P<0.001) or in controls with non-IgA nephropathy disease (14.8 [IQR 10.5-21.9] U/ml; P<0.001). Higher levels of poly-IgA immune complex were associated with lower eGFR and worse kidney outcome. Accuracy parameters and concordant statistics showed good discrimination between IgA nephropathy and healthy controls based on poly-IgA index levels (area under the curve [AUC], 0.78; 95% confidence interval [95% CI], 0.72 to 0.83; P<0.001), significantly outperforming galactose-deficient IgA1 levels (AUC, 0.70; P=0.05). Corticosteroid and immunosuppressant treatments lowered poly-IgA indices. After a recombinant CD89-directed workflow in conjunction with mass spectrometry, we also analyzed the molecular composition of IgA immune complex in patients with IgA nephropathy.ConclusionsHigher level of recombinant CD89-bound poly-IgA immune complex was associated with the severity of the disease and with treatment response to steroids and immunosuppressants.

Dataset Information

Key pathological features characterize minimal change disease-like IgA nephropathy.

Aims

Methods

Results

Conclusions

Publications

Key pathological features characterize minimal change disease-like IgA nephropathy.

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