A treatment dilemma in adult immunoglobulin A nephropathy: what is the appropriate target, preservation of kidney function or induction of clinical remission?

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Abstract

Immunoglobulin (Ig) A nephropathy is the most common type of glomerulonephritis worldwide. Data on its natural history suggest that approximately 40% of patients progress to end-stage renal failure after 20 years. Various therapies such as antiplatelet medication, fish oil, oral prednisolone, intravenous prednisolone, tonsillectomy, and tonsillectomy plus steroid pulse (TSP) have been proposed. Japanese nephrologists face challenging issues regarding this disease, such as the usefulness of the annual urinary screening system (kenshin) and kidney biopsies, the desire of patients and their families for treatment despite insufficient clinical evidence, and the risk of overtreatment with TSP versus the loss of a ‘golden period’ with late intervention. We review the current literature on tonsillectomy, steroid therapy, and TSP, which was first proposed in Japan, and present some perspectives on the treatment of IgA nephropathy.

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Corticosteroid effectiveness in IgA nephropathy: long-term results of a randomized, controlled trial.

Simeone Andrulli, C Pozzi, G B Fogazzi … (2003)

Proteinuria plays a causal role in the progression of IgA nephropathy (IgAN). A previous controlled trial showed that steroids are effective in reducing proteinuria and preserving renal function in patients with IgAN. The objective of this study was to evaluate the long-term effectiveness of steroids in IgAN, examine the trend of proteinuria during follow-up (starting from the hypothesis that the degree of reduction in proteinuria may influence IgAN outcome), and evaluate how histologic scores can influence steroid response. A secondary analysis of a multicenter, randomized, controlled trial of 86 adult IgAN patients who were receiving supportive therapy or intravenous methylprednisolone plus oral prednisone for 6 mo was conducted. Ten-year renal survival was significantly better in the steroid than in the control group (97% versus 53%; log rank test P = 0.0003). In the 72 patients who did not reach the end point (doubling in baseline serum creatinine), median proteinuria significantly decreased (1.9 g/24 h at baseline, 1.1 g/24 h after 6 mo, and 0.6 g/24 h after a median of 7 yr). In the 14 progressive patients, proteinuria increased from a median of 1.7 g/24 h at baseline to 2.0 g/24 h after 6 mo and 3.3 g/24 h after a median of 5 yr. Steroids were effective in every histologic class. Cox multivariate regression analyses showed that, in addition to steroids, a low baseline histologic score, a reduction in proteinuria after 6 mo, and no increase in proteinuria during follow-up all were independent predictors of a beneficial outcome. Steroids significantly reduce proteinuria and protect against renal function deterioration in IgAN. The histologic picture and proteinuria during early and late follow-up improve the prediction of outcome, but considerable variability remains outside the model.

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Tonsillectomy and steroid pulse therapy significantly impact on clinical remission in patients with IgA nephropathy.

Glenn Furuta, Kiyomi Abe, Y Taguma … (2001)

We conducted a retrospective investigation of renal outcome in 329 patients with immunoglobulin A (IgA) nephropathy with an observation period longer than 36 months (82.3 +/- 38.2 months) in our renal unit between 1977 and 1995. Clinical remission, renal progression, and the impact of covariates were estimated by Kaplan-Meier analysis and a Cox regression model. In 157 of 329 patients (48%), disappearance of urinary abnormalities (clinical remission) was obtained. None of these 157 patients showed progressive deterioration, defined as a 50% increase in serum creatinine (Scr) level from baseline, during the observation period. Conversely, in patients without clinical remission, the Kaplan-Meier estimate of probability of progressive deterioration was 21% +/- 5% at 10 years. In the multivariate Cox regression model with 13 independent covariates, initial Scr level, histological score, tonsillectomy, and high-dose methylprednisolone therapy had a significant impact on clinical remission, whereas proteinuria, age, sex, levels of hematuria, blood pressure, conventional steroid therapy, angiotensin-converting enzyme inhibitor therapy, and cyclophosphamide therapy had no significant effect. These findings indicate that interventions aimed at achieving clinical remission have provided encouraging results applicable to managing patients with IgA nephropathy.

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The natural history of immunoglobulin a nephropathy among patients with hematuria and minimal proteinuria.

Cheuk-Chun Szeto, Fernand Lai, Ka-Fai To … (2001)

To determine the natural history of immunoglobulin (Ig) A nephropathy among patients who presented with hematuria and minimal proteinuria, and factors associated with the development of adverse clinical events, such as proteinuria. In Hong Kong, all patients who present with isolated hematuria are referred for renal biopsy after urologic diseases are ruled out. We reviewed the clinical course of 72 consecutive patients with histologically confirmed IgA nephropathy who presented with hematuria and minimal proteinuria (0.4 g/day or less). All patients were normotensive and had normal renal function at presentation. Adverse events were defined as proteinuria greater than 1 g per day, hypertension, or impaired renal function (serum creatinine level 120 micromol/L or estimated creatinine clearance l g/day) to renal impairment was 84 months (range 56 to 132). In a multivariate analysis, age at presentation (relative risk [RR] per 10 years of age = 2.0; 95% confidence interval [CI], 1.2 to 3.4) and histologic grade (grade 2 versus grade 1, RR = 4.5; 95% CI, 1.7 to 12) were independent predictors of developing an adverse event. IgA nephropathy that presents with hematuria and minimal proteinuria is usually a progressive disease. Life-long follow-up with regular monitoring of blood pressure and proteinuria is recommended.

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Author and article information

Contributors

: +81-561-623311 , +81-561-626694 , imaihiro@aichi-med-u.ac.jp

Journal

Journal ID (nlm-ta): Clin Exp Nephrol

Journal ID (iso-abbrev): Clin. Exp. Nephrol

Title: Clinical and Experimental Nephrology

Publisher: Springer Japan (Japan )

ISSN (Print): 1342-1751

ISSN (Electronic): 1437-7799

Publication date (Electronic): 16 November 2011

Publication date PMC-release: 16 November 2011

Publication date (Print): April 2012

Volume: 16

Issue: 2

Pages: 195-201

Affiliations

Division of Nephrology and Rheumatology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute-cho, Aichi, 480-1195 Japan

Article

Publisher ID: 552

DOI: 10.1007/s10157-011-0552-8

PMC ID: 3328677

PubMed ID: 22086123

SO-VID: 0b2a4739-e5c3-4e9e-b165-3e8e0638904e

History

Date received : 19 July 2011

Date accepted : 12 October 2011

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ScienceOpen disciplines: Nephrology

Keywords: tonsillectomy plus steroid pulse therapy (tsp),tonsillectomy,iga nephropathy,steroid therapy

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ScienceOpen disciplines: Nephrology

Keywords: tonsillectomy plus steroid pulse therapy (tsp), tonsillectomy, iga nephropathy, steroid therapy

A treatment dilemma in adult immunoglobulin A nephropathy: what is the appropriate target, preservation of kidney function or induction of clinical remission?

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Most cited references 9

Corticosteroid effectiveness in IgA nephropathy: long-term results of a randomized, controlled trial.

Tonsillectomy and steroid pulse therapy significantly impact on clinical remission in patients with IgA nephropathy.

The natural history of immunoglobulin a nephropathy among patients with hematuria and minimal proteinuria.

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