Background: There is no clinical classification of immunoglobulin A nephropathy (IgAN) in clinical practice. In this study, we used receiver-operating characteristic (ROC) analysis to create accurate clinical grades based on clinical parameters associated with the development of end-stage renal disease (ESRD) in IgAN patients. Methods: We performed a retrospective analysis of 116 patients with IgAN. The association between clinical variables and progression to ESRD was examined. Results: Logistic regression analysis indicated that 24-hour urinary protein excretion (UPE) and the estimated glomerular filtration rate (eGFR) at the time of renal biopsy (RBx) were independently associated with the development of ESRD. When combining UPE and eGFR, the areas under the curve were superior to those for UPE or eGFR alone. Moreover, two-graph ROC analysis indicated that the threshold values for UPE and eGFR in predicting future ESRD were 1.0 g/day and 64.0 ml/min/1.73 m2, respectively. Of note, the patients were classified into 4 grades by levels of UPE and/or eGFR, and the OR for risk of ESRD rose significantly from grade I to grade IV. Conclusion: The combination of UPE and eGFR at the time of RBx can improve the predictive accuracy of risk for subsequent ESRD in IgAN patients.

Keywords:
Estimated glomerular filtration rate, End-stage renal disease, Immunoglobulin A nephropathy, Prognosis, Proteinuria, Receiver-operating characteristic analysis
1.
Donadio JV, Grande JP: IgA nephropathy. N Engl J Med 2002;347:738–748.
2.
Barratt J, Feehally J: Treatment of IgA nephropathy. Kidney Int 2006;69:1934–1938.
3.
Koyama A, Igarashi M, Kobayashi M: Natural history and risk factors for immunoglobulin A nephropathy in Japan. Research Group on Progressive Renal Diseases. Am J Kidney Dis 1997;29:526–532.
4.
D’Amico G: Natural history of idiopathic IgA nephropathy and factors predictive of disease outcome. Semin Nephrol 2004;24:179–196.
5.
Bartosik LP, Lajoie G, Sugar L, Cattran DC: Predicting progression in IgA nephropathy. Am J Kidney Dis 2001;38:728–735.
6.
Working Group of the International IgA Nephropathy Network and the Renal Pathology Society, Cattran DC, Coppo R, Cook HT, Feehally J, Roberts IS, Troyanov S, Alpers CE, Amore A, Barratt J, Berthoux F, Bonsib S, Bruijn JA, D’Agati V, D’Amico G, Emancipator S, Emma F, Ferrario F, Fervenza FC, Florquin S, Fogo A, Geddes CC, Groene HJ, Haas M, Herzenberg AM, Hill PA, Hogg RJ, Hsu SI, Jennette JC, Joh K, Julian BA, Kawamura T, Lai FM, Leung CB, Li LS, Li PK, Liu ZH, Mackinnon B, Mezzano S, Schena FP, Tomino Y, Walker PD, Wang H, Weening JJ, Yoshikawa N, Zhang H: The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification. Kidney Int 2009;76:534–545.
7.
Berthoux FC, Mohey H, Afiani A: Natural history of primary IgA nephropathy. Semin Nephrol 2008;28:4–9.
8.
Walsh M, Sar A, Lee D, Yilmaz S, Benediktsson H, Manns B, Hemmelgarn B: Histopathologic features aid in predicting risk for progression of IgA nephropathy. Clin J Am Soc Nephrol 2010;5:425–430.
9.
Hwang HS, Kim BS, Shin YS, Yoon HE, Song JC, Choi BS, Park CW, Yang CW, Kim YS, Bang BK: Predictors for progression in immunoglobulin A nephropathy with significant proteinuria. Nephrology 2010;15:236–241.
10.
Radford MG, Donadio JV, Bergstralh EJ, Grande JP: Predicting renal outcome in IgA nephropathy. J Am Soc Nephrol 1997;8:199–207.
11.
Donadio JV, Bergstralh EJ, Grande JP, Rademcher DM: Proteinuria patterns and their association with subsequent end-stage renal disease in IgA nephropathy. Nephrol Dial Transplant 2002;17:1197–1203.
12.
Reich HN, Troyanov S, Scholey JW, Cattran DC, Toronto Glomerulonephritis Registry: Remission of proteinuria improves prognosis in IgA nephropathy. J Am Soc Nephrol 2007;18:3177–3183.
13.
Linden A: Measuring diagnostic and predictive accuracy in disease management: an introduction to receiver operating characteristic (ROC) analysis. J Eval Clin Pract 2006;12:132–139.
14.
Robertson DM, Cahir N, Burger HG, Mamers P, McCloud PI, Pettersson K, McGuckin M: Combined inhibin and CA125 assays in the detection of ovarian cancer. Clin Chem 1999;45:651–658.
15.
Steinmetz T, Hellmich M, Neise M, Aldaud A, Lerchenmüller C, Tsamaloukas A, Fandel F, Weiligmann C, Totzke U, Schmitz S: Prediction of the responsiveness to treatment with erythropoiesis-stimulating factors: a prospective clinical study in patients with solid tumors. Oncologist 2007;12:748–755.
16.
Hallan SI, Ritz E, Lydersen S, Romundstad S, Kvenild K, Orth SR: Combining GFR and albuminuria to classify CKD improves prediction of ESRD. J Am Soc Nephrol 2009;20:1069–1077.
17.
Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Yamagata K, Tomino Y, Yokoyama H, Hishida A, Collaborators developing the Japanese equation for estimated GFR: Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis 2009;53:982–992.
18.
Schwartz GJ, Haycock GB, Edelmann CM Jr, Spitzer A: A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 1976;58:259–263.
19.
Greiner M, Sohr D, Göbel P: A modified ROC analysis for the selection of cut-off values and the definition of intermediate results of serodiagnostic tests. J Immunol Methods 1995;185:123–132.
20.
Coppo R, D’Amico G: Factors predicting progression in IgA nephropathies. J Nephrol 2005;18:503–512.
21.
Ruggenenti P, Perna A, Gherardi G, Benini R, Remuzzi G: Chronic proteinuric nephropathies: outocomes and response to treatment in a prospective cohort of 352 patients with different patterns of renal injury. Am J Kidney Dis 2000;35:1155–1165.
22.
Praga M, Gutiérrez E, González E, Morales E, Hernández E: Treatment of IgA nephropathy with ACE inhibitors: a randomized and controlled trial. J Am Soc Nephrol 2003;14:1578–1583.
23.
Li PK, Leung CB, Chow KM, Cheng YL, Fung SK, Mak SK, Tang AW, Wong TY, Yung CY, Yung JC, Yu AW, Szeto CC, HKVIN Study Group: Hong Kong study using valsartan in IgA nephropathy (HKVIN): a double-blind, randomized, placebo-controlled study. Am J Kidney Dis 2006;47:751–760.
24.
Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ, Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute, National High Blood Pressure Education Program Coordinating Committee: seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003;42:1206–1252.
25.
Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, Grassi G, Heagerty AM, Kjeldsen SE, Laurent S, Narkiewicz K, Ruilope L, Rynkiewicz A, Schmieder RE, Struijker Boudier HA, Zanchetti A, Vahanian A, Camm J, De Caterina R, Dean V, Dickstein K, Filippatos G, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano JL, Kjeldsen SE, Erdine S, Narkiewicz K, Kiowski W, Agabiti-Rosei E, Ambrosioni E, Cifkova R, Dominiczak A, Fagard R, Heagerty AM, Laurent S, Lindholm LH, Mancia G, Manolis A, Nilsson PM, Redon J, Schmieder RE, Struijker-Boudier HA, Viigimaa M, Filippatos G, Adamopoulos S, Agabiti-Rosei E, Ambrosioni E, Bertomeu V, Clement D, Erdine S, Farsang C, Gaita D, Kiowski W, Lip G, Mallion JM, Manolis AJ, Nilsson PM, O’Brien E, Ponikowski P, Redon J, Ruschitzka F, Tamargo J, van Zwieten P, Viigimaa M, Waeber B, Williams B, Zamorano JL, The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension, The Task Force for the Management of Arterial Hypertension of the European Society of Cardiology: 2007 Guidelines for the management of arterial hypertension. Eur Heart J 2007;28:1462–1536.
26.
Frimat L, Briançon S, Hestin D, Aymard B, Renoult E, Huu TC, Kessler M: IgA nephropathy: prognostic classification of end-stage renal failure. Nephrol Dial Transplant 1997;12:2569–2575.
27.
Pozzi C, Andrulli S, Del Vecchio L, Melis P, Fogazzi GB, Altieri P, Ponticelli C, Locatelli F: Corticosteroid effectiveness in IgA nephropathy: long-term results of a randomized, controlled trial. J Am Soc Nephrol 2004;15:157–163.
28.
Nachman PH, Glassock MD: IgA nephropathy. Nephrol Self Assess Program 2010;9:140–150.
29.
Lv J, Zhang H, Chen Y, Li G, Jiang L, Singh AK, Wang H: Combination therapy of prednisone and ACE inhibitor versus ACE-inhibitor therapy alone in patients with IgA nephropathy: a randomized controlled trial. Am J Kidney Dis 2009;53:26–32.
30.
Manno C, Torres DD, Rossini M, Pesce F, Schena FP: Randomized controlled clinical trial of corticosteroids plus ACE-inhibitors with long-term follow-up in proteinuric IgA nephropathy. Nephrol Dial Transplant 2009;24:3694–3701.
31.
Hanson RL, Imperatore G, Bennett PH, Knowler WC: Components of the ‘metabolic syndrome’ and incidence of type 2 diabetes. Diabetes 2002;51:3120–3127.
32.
Wang TJ, Gona P, Larson MG, Tofler GH, Levy D, Newton-Cheh C, Jacques PF, Rifai N, Selhub J, Robins SJ, Benjamin EJ, D’Agostino RB, Vasan RS: Multiple biomarkers for the prediction of first major cardiovascular events and death. N Engl J Med 2006;355:2631–2639.
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