Early treatment with corticosteroids ameliorates proteinuria, proliferative lesions, and mesangial phenotypic modulation in adult diffuse proliferative IgA nephropathy

Tanaka, Shōji; Nakanishi, Isao; Suzuki, Akira; Hayashi, Terumasa; Togawa, Masaki; Okada, Noriyuki; Imai, Enyu; Hori, Masatsugu; Tsubakihara, Yoshiharu

doi:10.1016/s0272-6386(00)70326-x

Cited by 111 publications

(81 citation statements)

References 31 publications

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“…Histologic lesions may be influenced by treatments. In a limited number of repeat biopsy studies, CS were shown to reduce mesangial 23 and endocapillary proliferation, tuft necrosis and glomerular crescents, interstitial monocyte infiltration and interstitial edema, and also lesions once thought to be irreversible, such as the percentage of segmentally sclerotic glomeruli and extent of interstitial fibrosis. 24 In this analysis of the VALIGA study, there was a nonsignificant trend for higher efficacy of CS in more advanced lesions.…”

Section: Discussionmentioning

confidence: 99%

Corticosteroids in IgA Nephropathy

Tesař

Troyanov

Bellur

et al. 2015

Journal of the American Society of Nephrology

199

161

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Current guidelines suggest treatment with corticosteroids (CS) in IgA nephropathy (IgAN) when proteinuria is persistently $1 g/d despite 3-6 months of supportive care and when eGFR is .50 ml/min per 1.73 m 2 . Whether the benefits of this treatment extend to patients with an eGFR#50 ml/min per 1.73 m 2 , other levels of proteinuria, or different renal pathologic lesions remains unknown. We retrospectively studied 1147 patients with IgAN from the European Validation Study of the Oxford Classification of IgAN (VALIGA) cohort classified according to the Oxford-MEST classification and medication used, with details of duration but not dosing. Overall, 46% of patients received immunosuppression, of which 98% received CS. Treated individuals presented with greater clinical and pathologic risk factors of progression. They also received more antihypertensive medication, and a greater proportion received renin angiotensin system blockade (RASB) compared with individuals without immunosuppressive therapy. Immunosuppression was associated with a significant reduction in proteinuria, a slower rate of renal function decline, and greater renal survival. Using a propensity score, we matched 184 subjects who received CS and RASB to 184 patients with a similar risk profile of progression who received only RASB. Within this group, CS reduced proteinuria and the rate of renal function decline and increased renal survival. These benefits extended to those with an eGFR#50 ml/min per 1.73 m 2 , and the benefits increased proportionally with the level of proteinuria. Thus, CS reduced the risk of progression regardless of initial eGFR and in direct proportion to the extent of proteinuria in this cohort.

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Section: Discussionmentioning

confidence: 99%

Corticosteroids in IgA Nephropathy

Tesař

Troyanov

Bellur

et al. 2015

Journal of the American Society of Nephrology

199

161

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“…Several studies have shown that corticosteroid treatment could decrease levels of urinary protein excretion and improve renal outcome in patients with IgAN (32-35). Shoji et al reported that early corticosteroid treatment for active and proliferative IgAN in adults was effective in reducing renal injury (36). Immunosuppressive treatment, including corticosteroids, is recommended for crescentic IgAN with active glomerular inflammation (35).…”

Section: Discussionmentioning

confidence: 99%

Relationships between Levels of Urinary Podocalyxin, Number of Urinary Podocytes, and Histologic Injury in Adult Patients with IgA Nephropathy

Asao

Asanuma

Kodama

et al. 2012

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Podocalyxin (PCX) is present on the apical cell membrane of podocytes and is shed in urine from injured podocytes. Urinary podocalyxin (u-PCX) is associated with severity of active glomerular injury in patients with glomerular diseases. This study examined the relationship between number of urinary podocytes, levels of u-PCX, and glomerular injury in adults with IgA nephropathy (IgAN).Design, setting, participants, & measurements Urine samples voided in the morning on the day of biopsy were obtained from 51 patients with IgAN (18 men and 33 women; mean age, 31 years). All renal biopsy specimens were analyzed histologically. Pathologic variables of IgAN were analyzed per Shigematsu classification, the Oxford classification of IgAN, and the Clinical Guidelines of IgAN in Japan. Levels of u-PCX were measured by sandwich ELISA.Results Histologic analysis based on Shigematsu classification revealed a significant correlation between levels of u-PCX and severity of acute extracapillary abnormalities (r=0.72; P,0.001), but levels of urinary protein excretion did not correlate with acute glomerular abnormalities. Levels of urinary protein excretion in patients with segmental sclerosis (n=19) were higher than in patients without (n=22 Conclusions Levels of u-PCX and the number of urinary podocytes are associated with histologic abnormalities in adults with IgAN.

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“…Moreover, there was a reduction in glomerulosclerosis, tubular atrophy, or interstitial fibrosis. In a similar study, Shoji et al (51) …”

Section: Effect Of Immunosuppressive Therapy On Renal Histologymentioning

confidence: 71%

Idiopathic IgA Nephropathy

Tumlin

Madaio

Hennigar

2007

Clinical Journal of the American Society of Nephrology

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Epidemiology and Natural HistoryIgA nephropathy (IgAN) is considered to be the most common form of glomerulonephritis in the world (1). Although IgAN is prevalent in all ethnic groups, Japan and Korea have some of the highest recorded incidences. For example, approximately 50% of new cases of glomerulonephritis and 40% of all ESRD in Japan are due to IgAN. This is in contrast to the United States and Western Europe, where IgAN accounts for 10 and 30% of glomerulonephritis, respectively (2). Although these disparities may reflect differences in public health awareness or the willingness of nephrologists to perform diagnostic biopsies, certain populations seem to have a genetic predisposition to the development of IgAN (1).The clinical presentation of a typical flair includes the development of painless hematuria concurrent with the onset of a viral pharyngitis, gastroenteritis, or pneumonia. Approximately 30 to 40% of patients with IgAN will present with gross hematuria and renal dysfunction. Praga et al. (3) reviewed the clinical course of 29 patients with gross hematuria secondary to IgAN and demonstrated that 37% developed transient renal failure. Although early renal dysfunction was more common in patients with gross hematuria, complete recovery was experienced by all 29 patients. These results are consistent with previous observations that patients with intermittent gross hematuria do not develop proteinuria and generally have a better overall prognosis (4).IgAN has been generally regarded as a benign form of glomerulonephritis, with approximately 25 to 30% of patients reaching ESRD after 10 yr (5). Clinical risk factors linked to progressive IgA disease include hypertension, proteinuria Ͼ1.0 g/24 h, male gender, and persistent microscopic hematuria, (4 -6). Clinical Presentation of Crescentic/ Proliferative IgANSpecific histologic features are associated with a poor prognosis, including cellular crescents, endocapillary proliferation, and karyorrhexis. It is interesting that these histologic signs often do not correlate with existing clinical risk factors (7). For example, Almartine et al. (8) examined the biopsies of 282 patients with IgAN and demonstrated that the presence of crescents did not correlate with hypertension or proteinuria. In contrast, Welch and colleagues (9 -11) reported that Ͼ75% of patients with IgAN and endocapillary proliferation had hypertension at presentation, whereas up to 20% presented with accelerated hypertension (mean arterial pressure Ͼ150 mmHg). Moreover, Tumlin et al. (12,13) reviewed the clinical presentation of 20 patients who had IgAN with at least 10% cellular crescents and demonstrated that all had hypertension (mean arterial pressure Ͼ90 mmHg) with Ͼ1.0 g of proteinuria, and an additional 33% presented with nephrotic-range proteinuria.

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Early treatment with corticosteroids ameliorates proteinuria, proliferative lesions, and mesangial phenotypic modulation in adult diffuse proliferative IgA nephropathy

Cited by 111 publications

References 31 publications

Corticosteroids in IgA Nephropathy

Corticosteroids in IgA Nephropathy

Relationships between Levels of Urinary Podocalyxin, Number of Urinary Podocytes, and Histologic Injury in Adult Patients with IgA Nephropathy

Idiopathic IgA Nephropathy

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