Interstitial Inflammatory and Chronic Tubulointerstitial Lesions in Lupus Nephritis: Comparison with those in IgA Nephropathy

Lupus ◽  
1993 ◽  
Vol 2 (1_suppl) ◽  
pp. 261-268 ◽  
Author(s):  
Tatsuo Yamamoto ◽  
Mitsumasa Nagase ◽  
Akira Hishida ◽  
Nishio Honda
Keyword(s):  
Lupus Nephritis ◽  
Iga Nephropathy ◽  
Immune Complexes ◽  
Prognostic Significance ◽  
Underlying Disease ◽  
Inflammatory Lesions ◽  
Tubulointerstitial Lesions ◽  
Glomerular Lesions ◽  
Renal Prognosis

The significance of interstitial inflammatory and chronic tubulointerstitial lesions was studied in relation to the severity of glomerular lesions in 62 patients with lupus nephritis and 88 with IgA nephropathy. Severe interstitial inflammatory and chronic tubulointerstitial lesions were found in patients with severe glomerular lesions in both lupus nephritis and IgA nephropathy. In such cases, the serum creatinine levels at biopsy were high and the renal prognosis was poor regardless of the underlying disease (lupus nephritis or IgA nephropathy). No IgA nephropathy patients with nil or mild glomerular lesions had moderate or severe interstitial inflammatory and/or chronic tubulointerstitial lesions. In contrast, predominantly severe interstitial inflammatory lesions were found in 36% of lupus nephritis patients with nil or mild glomerular lesions. The prevalence of interstitial immune complexes deposition was markedly high in those with predominant interstitial inflammatory lesions. However, the severity of chronic tubulointerstitial lesions was mild and renal function did not deteriorate in the mean follow-up periods of 68.6 months. It is suggested that, besides the tubulointerstitial lesions attributable to the severe concomitant glomerular damage, the interstitial deposition of immune complexes per se plays a pathogenic role in the interstitial inflammatory lesions in lupus nephritis. Its prognostic significance, however, was considered to be minor.

Interstitial Inflammatory and Chronic Tubulointerstitial Lesions in Lupus Nephritis: Comparison with Those in IgA Nephropathy

Lupus ◽  
1993 ◽  
Vol 2 (4) ◽  
pp. 261-268 ◽  
Author(s):  
Tatsuo Yamamoto ◽  
Mitsumasa Nagase ◽  
Akira Hishida ◽  
Nishio Honda
Keyword(s):  
Lupus Nephritis ◽  
Iga Nephropathy ◽  
Tubulointerstitial Lesions

scholarly journals Expression of types I, II, and III TGF-beta receptors in human glomerulonephritis.

1998 ◽  
Vol 9 (12) ◽  
pp. 2253-2261
Author(s):  
T Yamamoto ◽  
T Watanabe ◽  
N Ikegaya ◽  
Y Fujigaki ◽  
K Matsui ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Lupus Nephritis ◽  
Iga Nephropathy ◽  
Membranoproliferative Glomerulonephritis ◽  
Type I ◽  
Tgf Beta ◽  
Matrix Deposition ◽  
Peritubular Capillaries ◽  
Tubulointerstitial Lesions ◽  
Beta Receptors

Protein and mRNA expression of transforming growth factor-beta (TGF-beta) receptor type I (TbetaRI), type II (TbetaRII), and type III (TbetaRIII) were studied in serial sections of kidney samples obtained from patients with glomerulonephritis. In minimal change disease, weak expression of TbetaRI and TbetaRII was observed mainly in glomerular endothelial cells, peritubular capillaries, and interstitial arteriolar endothelial cells, whereas TbetaRIII expression was found mainly in the interstitium. Expression of all three TGF-beta receptors (TbetaR) was increased remarkably in glomerular and Bowman's capsular cells comprising the tuft adhesions to Bowman's capsules in glomerulonephritis with increased matrix accumulation, including IgA nephropathy, lupus nephritis, focal and segmental glomerulosclerosis, myeloperoxidase-antineutrophil cytoplasmic antibody-associated crescentic glomerulonephritis, and membranoproliferative glomerulonephritis. Increased expression of the three TbetaR was also seen in glomerular epithelial cells in the vicinity of glomerulosclerotic lesions, in crescent cells, and in some tubules and infiltrative mononuclear cells found in the periglomerular and tubulointerstitial lesions with increased matrix deposition. In contrast, no remarkable TbetaRII expression was noted in mesangial proliferative lesions in IgA nephropathy, lupus nephritis, and membranoproliferative glomerulonephritis. These data suggest that distinctive modulation of TbetaR expression may be involved in the development of adhesive, sclerotic, and proliferative renal lesions in human glomerulonephritis.

Prognostic Significance of Circulating Immune Complexes in a Long-Term Follow-Up of Breast Cancer Patients

Oncology ◽  
1988 ◽  
Vol 45 (5) ◽  
pp. 337-343 ◽  
Author(s):  
Rosario Vincenzo laffaioli ◽  
Armando Bianchin ◽  
Giuseppina Ruggiero ◽  
Giuseppe Pirozzi ◽  
Achille Ungaro ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Immune Complexes ◽  
Prognostic Significance ◽  
Circulating Immune Complexes ◽  
Breast Cancer Patients ◽  
Long Term Follow Up

Prognostic significance of persistent massive proteinuria in IgA nephropathy: 10-year follow-up study of 366 cases

Nephrology ◽  
2001 ◽  
Vol 6 (s1) ◽  
pp. A23-A24 ◽  
Author(s):  
Y Kobayashi ◽  
Y Hiki ◽  
T Sano ◽  
K Hashizume ◽  
T Matsuo ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Prognostic Significance ◽  
Follow Up Study

scholarly journals Classifying Lupus Nephritis: An Ongoing Story

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Saba Kiremitci ◽  
Arzu Ensari
Keyword(s):  
Lupus Nephritis ◽  
Prognostic Significance ◽  
World Health ◽  
Clinicopathological Correlation ◽  
New Classification ◽  
Tubulointerstitial Lesions ◽  
The World ◽  
Weak Points ◽  
Health Organization

The role of the renal biopsy in lupus nephritis is to provide the diagnosis and to define the parameters of prognostic and therapeutic significance for an effective clinicopathological correlation. Various classification schemas initiated by World Health Organization in 1974 have been proposed until the most recent update by International Society of Nephrology/Renal Pathology Society in 2004. In this paper, we reviewed the new classification system with the associated literature to highlight the benefits and the weak points that emerged so far. The great advantage of the classification emerged to provide a uniform reporting for lupus nephritis all over the world. It has provided more reproducible results from different centers. However, the studies indicated that the presence of glomerular necrotizing lesion was no longer significant to determine the classes of lupus nephritis leading to loss of pathogenetic diversity of the classes. Another weakness of the classification that also emerged in time was the lack of discussions related to the prognostic significance of tubulointerstitial involvement which was not included in the classification. Therefore, the pathogenetic diversity of the classification still needs to be clarified by additional studies, and it needs to be improved by the inclusion of the tubulointerstitial lesions related to prognosis.

scholarly journals THU0248 GLOMERULAR AND TUBULOINTERSTITIAL LESIONS IN PER-PROTOCOL REPEAT BUT NOT BASELINE KIDNEY BIOPSY PORTEND RELAPSE AND LONG-TERM RENAL FUNCTION IMPAIRMENT, RESPECTIVELY, IN INCIDENT CASES OF PROLIFERATIVE LUPUS NEPHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 351.2-351
Author(s):  
I. Parodis ◽  
C. Adamichou ◽  
S. Aydin ◽  
A. Gomez ◽  
N. Demoulin ◽  
...  
Keyword(s):  
Renal Function ◽  
Lupus Nephritis ◽  
Clinical Response ◽  
Activity Index ◽  
Repeat Biopsy ◽  
Renal Function Impairment ◽  
Tubulointerstitial Lesions ◽  
Function Impairment ◽  
Glomerular Lesions

Background:In patients with lupus nephritis (LN), clinical response to treatment and renal histopathology have been shown to be discordant. No clinical or laboratory markers have to date been shown to reliably portend renal prognosis, in particular renal function impairment.Objectives:To investigate whether per-protocol repeat renal biopsies are predictive of LN relapses and long-term impairment of renal function.Methods:Forty-two patients with an incident biopsy-proven active proliferative (class III/IV ± V) LN from the LN database of the Université catholique de Louvain were included in the present retrospective study. Per-protocol repeat kidney biopsies were performed in all patients after a median time of 24.3 (IQR: 21.3–26.2) months. The NIH activity index (AI) and chronicity index (CI) scores were assessed in both baseline and repeat biopsies. We defined acute glomerular lesions as cellular proliferation, fibrinoid necrosis or karyorrhexis, cellular crescents, hyaline thrombi or wire loops, and leucocyte infiltration, and chronic glomerular lesions as glomerular sclerosis and fibrous crescents, in alignment with the NIH activity and chronicity indices. Similarly, we defined acute tubulointerstitial lesions as mononuclear cell infiltration and chronic tubulointerstitial lesions as interstitial fibrosis and tubular atrophy.Results:Despite a moderate correlation between urinary protein/creatinine (U-P/C) ratios and AI scores at repeat biopsy (r=0.48; P=0.001), ten patients (23.8%) with U-P/C ratios <1.0 g/g still had a high degree of histological activity (AI score >3). High AI scores in repeat (but not baseline) kidney biopsies were associated with an increased probability and/or shorter time to renal relapse (N=11) following the repeat biopsy (HR: 1.2; 95% CI: 1.1–1.3; P=0.007), independently of proteinuria levels. This association remained significant for the NIH activity index items within the glomerular but not the tubulointerstitial compartment of the kidney biopsies. High NIH CI scores in repeat (but not baseline) kidney biopsies were associated with a sustained increase in serum creatinine levels corresponding to ≥120% of the baseline value (HR: 1.8; 95% CI: 1.1–2.9; P=0.016) through a median follow-up time of 131.5 (IQR: 73.8–178.2) months, being the case also for acute and chronic tubulointerstitial lesions in repeat but not baseline kidney biopsies.Conclusion:Our results highlight the usefulness of per-protocol repeat biopsies as an integral part of the treatment evaluation, also in patients who have shown adequate clinical response. Glomerular lesions consistent with active renal disease portend LN relapses, while tubulointerstitial lesions consistent with active disease and chronic damage portent long-term renal function impairment.Disclosure of Interests:Ioannis Parodis: None declared, Christina Adamichou: None declared, Selda Aydin: None declared, Alvaro Gomez: None declared, Nathalie Demoulin: None declared, Julia Weinmann-Menke: None declared, Frederic Houssiau Grant/research support from: UCB, Consultant of: GSK, Farah Tamirou: None declared

scholarly journals Experimental IgA nephropathy.

1979 ◽  
Vol 150 (5) ◽  
pp. 1161-1173 ◽  
Author(s):  
A Rifai ◽  
P A Small ◽  
P O Teague ◽  
E M Ayoub
Keyword(s):  
Iga Nephropathy ◽  
Immune Complex ◽  
Immune Complexes ◽  
Secretory Iga ◽  
Glomerular Lesions ◽  
Glomerular Deposits ◽  
Focal Glomerulonephritis ◽  
Iga Immune Complexes

An animal model for IgA immune complex nephritis was developed. IgA immune complexes formed in vitro with an IgA anti-dinitrophenyl (DNP) derived from MOPC-315 plasmacytoma, and dinitrophenylated bovine serum albumin (DNP-BSA) produced mild focal glomerulonephritis in mice. Similar, but more severe pathological changes were produced with complexes formed in vivo either in normal mice or MOPC-315 tumor-bearing mice. In contrast to the focal nature of the PAS-positive glomerular lesions observed by light microscopy, immunofluorescent examination revealed IgA deposits in all glomeruli. This discrepancy between immunofluorescent and histopathologic findings as well as the distribution of the immune complexes within the affected glomeruli, are some of the features which bear resemblance between this experimental model and human IgA nephropathy. Fixation of complements by DNP-BSA-IgA immune complexes, formed in vitro or in vivo, was shown to occur in the glomeruli of mice with IgA immune complex nephropathy. The pattern of C3 glomerular deposits was similar to that of IgA. However, complement proved to be nonessential for complex deposition. This conclusion is based on the observation that decomplemented mice, although showing no deposition of C3 in their glomerulus, developed glomerular immunohistological changes similar to those observed in experimental mice that were not decomplemented. Polymeric IgA was observed to be critical for renal deposition of complexes and induction of nephritic histological changes. In contrast, monomeric IgA immune complexes failed to produce glomerular deposits. This finding raises the possibility that secretory IgA, which is predominantly polymeric, may play a role in human IgA-associated glomerulonephritis.

scholarly journals Serum IL-18 Is Closely Associated with Renal Tubulointerstitial Injury and Predicts Renal Prognosis in IgA Nephropathy

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Beili Shi ◽  
Zhaohui Ni ◽  
Liou Cao ◽  
Minjie Zhou ◽  
Shan Mou ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Renal Outcome ◽  
Tubulointerstitial Injury ◽  
Baseline Serum ◽  
Protein Excretion ◽  
Kaplan Meier ◽  
Tubulointerstitial Damage ◽  
Renal Prognosis ◽  
Cox Analysis

Background. IgA nephropathy (IgAN) was thought to be benign but recently found it slowly progresses and leads to ESRD eventually. The aim of this research is to investigate the value of serum IL-18 level, a sensitive biomarker for proximal tubule injury, for assessing the histopathological severity and disease progression in IgAN.Methods. Serum IL-18 levels in 76 IgAN patients and 36 healthy blood donors were measured by ELISA. We evaluated percentage of global and segmental sclerosis (GSS) and extent of tubulointerstitial damage (TID). The correlations between serum IL-18 levels with clinical, histopathological features and renal prognosis were evaluated.Results. The patients were38.85±10.95years old, presented with 2.61 (1.43∼4.08) g/day proteinuria. Serum IL-18 levels were significantly elevated in IgAN patients. Baseline serum IL-18 levels were significantly correlated with urinary protein excretion (r=0.494,P=0.002), Scr (r=0.61,P<0.001), and eGFR (r=−0.598,P<0.001). TID scores showed a borderline significance with serum IL-18 levels (r=0.355,P=0.05). During follow-up, 26 patients (34.21%) had a declined renal function. Kaplan-Meier analysis found those patients with elevated IL-18 had a significant poor renal outcome (P=0.03), and Cox analysis further confirmed that serum IL-18 levels were an independent predictor of renal prognosis (β=1.98,P=0.003).

scholarly journals The levels of urinary joining chain containing IgG immune complexes are associated with disease severity in IgA nephropathy

2019 ◽  
Author(s):  
Guanhong Li ◽  
Cai Yue ◽  
Xiaohong Fan ◽  
Yubing Wen ◽  
Gang Chen ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Iga Nephropathy ◽  
Disease Severity ◽  
Immune Complexes ◽  
Kidney Diseases ◽  
Enzyme Linked Immunosorbent Assay ◽  
Creatinine Ratio ◽  
Operating Characteristics ◽  
Potential Biomarker ◽  
Tubulointerstitial Lesions

Abstract Background: Circulating levels of aberrantly glycosylated IgA1 and its immune complexes (IgA/IgG-IC) are elevated and correlated with disease severity in IgA nephropathy (IgAN). The pathologic IgA containing immune complexes deposits in the kidney were found to be in dimeric or polymeric forms, suggesting that those deposited IgA immune complexes contain joining chain, which is critical for the multimerization and transportation of IgA. Both the dimeric IgA and polymeric IgA can cause renal damage by inducing the release of cytokines from mesangial cells. We aimed to investigate the urinary J chain containing IgG immune complexes/creatinine ratio (UJGCR) and analyze its relationship with disease severity in IgAN. Methods: The UJGCR were measured by sandwich enzyme linked immunosorbent assay in 26 patients with IgAN, 31 patients with other kidney diseases and 32 healthy volunteers. Results: The levels of UJGCR were higher in patients with IgAN than that in non-IgAN patients ( P =0.006) and healthy volunteers ( P <0.0001). Importantly, receiver operating characteristics curve analysis confirmed that UJGCR had good discrimination between non-IgAN patients and IgAN patients. The levels of UJGCR positively correlated with 24-hour urinary protein excretion (r=0.63, P =0.0006), serum creatinine (r=0.55, P =0.003), and negatively correlated with estimated glomerular filtration rate (r= -0.61, P =0.0008) in IgAN. Furthermore, the levels of UJGCR were higher in IgAN patients with IgA mesangial deposition of (+/++) than patients with (+++/++++). And IgAN patients with tubular atrophy/interstitial fibrosis showed higher levels of UJGCR than that without ( P =0.03). Similarly, the levels of urinary IgA-IgG/creatinine ratio (UAGCR) were also found to be elevated and associated with clinical and pathological parameters as UJGCR in IgAN. Besides, significant correlation between the levels of UJGCR and UAGCR was shown, suggesting UJGCR was mainly composed of J-IgA-IgG. Conclusions: The levels of UJGCR are associated with disease severity in IgAN. UJGCR is a potential biomarker for both glomerular and tubulointerstitial lesions in IgAN.

P0313POLYCLONAL FREE LIGHT CHAINS IN IGA-NEPHROPATHY: CORRELATION WITH CLINICAL AND MORPHOLOGICAL PARAMETERS AND PROGNOSTIC SIGNIFICANCE.

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Anna Churko ◽  
Maria Khrabrova ◽  
Vasiliy Sipovskii ◽  
Alexei Smirnov
Keyword(s):  
Iga Nephropathy ◽  
Prognostic Significance ◽  
Light Chains ◽  
Morphological Parameters ◽  
Free Light Chains ◽  
Ckd Progression ◽  
Tubular Atrophy ◽  
Cox Regression Analysis ◽  
Interstitial Inflammation

Abstract Background and Aims Mechanisms of kidney injury by monoclonal free light chains in myeloma kidney are well established. The role polyclonal free light chains (pFLC) in pathogenesis of renal interstitial inflammation and fibrosis in primary glomerulonephritis is still poorly investigated. We hypothesize that increased level of pFLC could have the similar role in activation of interstitial inflammation and fibrosis formation and impact chronic kidney disease (CKD) progression in the most prevalent form of chronic glomerulonephritis - IgA-nephropathy (IgAN). The aim of this retrospective study was to analyze the association of pFLC kappa (pFLC-κ) and lambda (pFLC-λ) assessed in serum by Freelite® with clinical and morphological parameters and CKD progression in IgA-nephropathy cohort. Method In this study we enrolled 23 patients with biopsy-confirmed diagnosis of IgAN. pFLC-κ and pFLC-λ levels were assessed in all cases at the time of kidney biopsy (KBx) by Freelite method. Normal range for pFLC-κ and pFLC-λ was 3,3-19,4 mg/l and 5,7-26,3 mg/l, respectively. The following clinical parameters were evaluated at the time of KBx: estimated glomerular filtration rate (eGFR) by CKD-EPI, daily proteinuria, serum albumin and microhematuria. Morphological findings were investigated by light and immunofluorescence (IgA, IgM, IgG, C3, C1, lambda, kappa, fibrinogen) microscopy. Oxford MEST-C score was evaluated as well as % of sclerotic glomeruli. Additionally we semiquantitatively measured (0- absent, 1- mild, 2 – moderate, 3 - severe) mesangial proliferation, endocapillary proliferation, glomerular basement membrane (GBM) thickening, interstitial inflammation, interstitial edema, tubular atrophy (TA), peritubular capillaritis (PTC), interstitial fibrosis (IF) according to currently accepted criteria. The demographic, clinical and morphological parameters at the time of KBx are presented in Table 1. Patients were treated with nephroprotective agents (n=23) and steroids/cyclophosphamide (n=21). Correlation between parameters were assessed by Spearman’s coefficient. Progression of CKD was determined as decline of eGFR &gt;25% from the initial level at the end of follow-up period. Prognostic analysis was performed with Cox proportional hazards regression. Median follow-up was 28 (7; 37) months. Results Correlations between clinical and morphological parameters and pFLC levels are presented in Table 2. Univariate Cox regression analysis has shown that pFLC-κ (Exp(β)=1,051; 95% CI: 1,001-1,104, p=0,045) and FLC- λ (Exp(β)=1,040; 95% CI: 1,001-1,081, p=0,044) as well as other well-known clinical (daily proteinuria (Exp(β)=1,177; 95% CI: 1,003-1,382, p=0,045), eGFR at the KBx time (Exp(β)=2,981; 95% CI:1,112-20,124, p=0,042)) and morphological parameters (% of sclerotic glomeruli (Exp(β)=1,031; 95% CI: 1,001-1,062, p=0,046), T-score (Expβ=10,784; 95% СI: 1,364-85,246, p=0,024) are associated with CKD progression. Conclusion In IgAN higher levels of pFLC, both kappa and lambda, are associated with renal interstitial inflammation and fibrosis, tubular atrophy and chronic glomerular injury and could be used as predictors of CKD progression. Mechanisms of pFLC effects on the formation of renal tubular and interstitial inflammation and fibrosis require further studies.

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