Resistance factors for the treatment of immunoglobulin <scp>A</scp> nephropathy with diffuse mesangial proliferation

Kawasaki, Yukihiko; Suyama, Kazuhide; Miyazaki, Kyohei; Kanno, Shuto; Ono, Atsushi; Suzuki, Yuichi; Sato, Masatoki; Hashimoto, Koichi

doi:10.1111/nep.12232

Cited by 14 publications

(16 citation statements)

References 25 publications

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“…In paediatric IgAN, infiltrating interstitial and glomerular macrophages are associated with unfavourable evolution,persistent inflammatory activation and proteinuria . We have demonstrated that E score largely reflects glomerular inflammation and that CD68 + cells participate in renal infiltrates; median endocapillary CD68 + counts were associated with the extent of endocapillary hypercellularity.…”

Section: Discussionmentioning

confidence: 81%

Relationship between renal CD68⁺ infiltrates and the Oxford Classification of IgA nephropathy

et al. 2019

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Aims The Oxford Classification E score (endocapillary hypercellularity) predicts renal functional decline in IgA nephropathy (IgAN) patients free from steroid/immunosuppressive (IS) therapy, but is poorly reproducible. We hypothesise that endocapillary hypercellularity reflects glomerular inflammation and that the presence of CD68‐positive cells is a more robust marker of E score. Methods and results CD68‐positive cells were quantified in glomeruli and tubulointerstitium in biopsies from 118 IgAN patients, and cell counts were correlated with the criteria of the Oxford Classification, assigned on PAS‐stained serial sections. There was a strong correlation between median glomerular CD68 count and the percentage of glomeruli showing endocapillary hypercellularity (r = 0.67; P < 0.001; r2 = 0.45), while there was no correlation between CD68‐positive cells and mesangial hypercellularity, % segmental sclerosis, % of crescents and % tubular atrophy/interstitial fibrosis (TA/IF). ROC curve analysis demonstrated that a maximum glomerular CD68 count of 6 is the best cut‐off for distinguishing E0 from E1 (sensitivity 94.1%, specificity 71%, area under the curve = 89%). Identification of biopsies with a maximum glomerular CD68‐count >6 was reproducible (kappa score 0.8), and there was a strong correlation between glomerular CD68 counts obtained by conventional light microscopy and by image analysis (r = 0.80, r2 = 0.64, P < 0.0001). Digital image analysis revealed that tubulointerstitial CD68‐positive cells correlated moderately with % TA/IF (r = 0.59, r2 = 0.35, P < 0.001) and GFR at the time of biopsy (r = 0.54, r2 = 0.29, P < 0.0001), but not with mesangial and endocapillary hypercellularity. Conclusions While glomerular CD68‐positive cells emerge as markers of endocapillary hypercellularity, their tubulointerstitial counterparts are associated with chronic damage.

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Section: Discussionmentioning

confidence: 81%

Relationship between renal CD68⁺ infiltrates and the Oxford Classification of IgA nephropathy

et al. 2019

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“…We also found that 89% of children with severe IgAN treated with combination therapy, consisting of prednisolone, mizoribine, warfarin, and dipyridamole, had no or only mild proteinuria, and reported that combination therapy had improved the long -term outcome of IgAN 10) . In other words, these findings suggested that few patients 72 Y.…”

Section: Discussionmentioning

confidence: 81%

“…The prognosis of most severe cases of pediatric IgAN treated with multi -drugs combination therapy is good ; however, some patients with severe IgAN experience recurrence after combination therapy or resistance to treatment. We also showed that 11% of children with severe IgAN treat-Long prognosis of tonsillectomy plus pulse therapy ed with combination therapy, consisting of prednisolone, mizoribine, warfarin, and dipyridamole, had the relapse of IgAN 10) , and there have been few reports on adequate treatments for these IgAN patients.…”

Section: Introductionmentioning

confidence: 99%

Successful therapy with tonsillectomy plus pulse therapy for the relapse of pediatric IgA nephropathy treated with multi-drugs combination therapy

Sakai

Kawasaki

Waragai

et al. 2016

FJMS

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Immunoglobulin A nephropathy (IgAN) is the most common form of chronic glomerulonephritis worldwide. In Japan, the treatment for use as an initial therapy was established in Guidelines for the Treatment of Childhood IgA nephropathy ; however, no rescue therapy for recurrent or steroidresistant pediatric IgAN was established. We report here a 15 -year -old boy with severe IgAN, who was treated with combination therapy involving prednisolone, mizoribine, warfarin, and dilazep dihydrochloride for 2 years. The response to the combination therapy was good and both proteinuria and hematuria disappeared. The pathological findings at the second renal biopsy were improved and PSL was discontinued. However, due to nonadherence to the treatment regimen and tonsillitis, macrohematuria and an increase of proteinuria were again observed and the pathological findings at the third renal biopsy showed clear deterioration. The patient was, therefore, diagnosed with recurrent IgAN. Tonsillectomy plus methylprednisolone pulse therapy (TMP) was performed as a rescue therapy for the recurrence of severe IgAN. Both the proteinuria or hematuria subsequently disappeared, and no proteinuria or hematuria has been observed and kidney function has remained normal during a 5 -year follow -up. The patient experienced no severe side effects associated with the drug regimens. In conclusion, our case suggests that TMP may be an effective and useful rescue therapy for recurrent IgAN after multi -drug combination therapy.

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“…Yoshikawa et al . reported the beneficial effects of multiple‐drug therapy consisting of prednisolone, azathioprine, heparin‐warfarin, and dipyridamole in the treatment of severe pediatric IgAN, and we previously reported that prednisolone, warfarin, and dipyridamole therapy combined with mizoribine (PWDM) was effective in ameliorating proteinuria and histological severity in children with IgAN on short‐term follow up, and showed that only 11% of children with severe IgAN treated with PWDM had IgAN relapse at long‐term follow up …”

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confidence: 89%

“…There have been many reports on the treatment of pediatric IgAN. Since 1990, corticosteroids, immunosuppressive agents, antiplatelet drugs, and anticoagulation agents have been used alone or in combination to treat IgAN . Yoshikawa et al .…”

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confidence: 99%

Long‐term follow up of pediatric immunoglobulin A nephropathy treated with tonsillectomy plus methylprednisolone pulse therapy

Kawasaki

Maeda

Kanno

et al. 2016

Pediatrics International

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Resistance factors for the treatment of immunoglobulin A nephropathy with diffuse mesangial proliferation

Cited by 14 publications

References 25 publications

Relationship between renal CD68⁺ infiltrates and the Oxford Classification of IgA nephropathy

Relationship between renal CD68⁺ infiltrates and the Oxford Classification of IgA nephropathy

Successful therapy with tonsillectomy plus pulse therapy for the relapse of pediatric IgA nephropathy treated with multi-drugs combination therapy

Long‐term follow up of pediatric immunoglobulin A nephropathy treated with tonsillectomy plus methylprednisolone pulse therapy

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Resistance factors for the treatment of immunoglobulin A nephropathy with diffuse mesangial proliferation

Cited by 14 publications

References 25 publications

Relationship between renal CD68+ infiltrates and the Oxford Classification of IgA nephropathy

Relationship between renal CD68+ infiltrates and the Oxford Classification of IgA nephropathy

Successful therapy with tonsillectomy plus pulse therapy for the relapse of pediatric IgA nephropathy treated with multi-drugs combination therapy

Long‐term follow up of pediatric immunoglobulin A nephropathy treated with tonsillectomy plus methylprednisolone pulse therapy

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Relationship between renal CD68⁺ infiltrates and the Oxford Classification of IgA nephropathy

Relationship between renal CD68⁺ infiltrates and the Oxford Classification of IgA nephropathy