BMC Nephrology | |
Fractional excretion of IgG in idiopathic membranous nephropathy with nephrotic syndrome: a predictive marker of risk and drug responsiveness | |
Omran Bakoush3  Giuseppe D’Amico5  Maurizio Gallieni2  Anna-Lena Berg1  Rafid Tofik1  Daniela Casellato2  Virginia Rizza4  Claudio Bazzi5  | |
[1] Department of Nephrology, Lund University, Lund, Sweden;Nephrology and Dialysis Unit, Azienda Ospedaliera Ospedale San Carlo Borromeo, Milan, Italy;Department of Internal Medicine, UAE University, Al Ain, United Arab Emirates;Biochemical Laboratoryt, Azienda Ospedaliera Ospedale San Carlo Borromeo, Milan, Italy;D’Amico Foundation for Renal Diseases Research, Milan, Italy | |
关键词: Treatment outcome; Proteinuria; Nephrotic syndrome; ESRD; Cyclophosphamide; Steroids; Immunoglobulin G; Idiopathic membranous glomerulonephritis; Albuminuria; | |
Others : 1082688 DOI : 10.1186/1471-2369-15-74 |
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received in 2014-03-24, accepted in 2014-05-01, 发布年份 2014 | |
【 摘 要 】
Background
Treatment of idiopathic membranous nephropathy with nephrotic syndrome is still controversial. There is currently little known about the clinical use of renal biomarkers which may explain contradictory results obtained from clinical trials. In order to assess whether IgG-uria can predict the outcome in membranous nephropathy, we examined the value of baseline EF-IgG in predicting remission and progression of nephrotic syndrome.
Methods
In a prospective cohort of 84 (34 female) idiopathic membranous nephropathy patients with nephrotic syndrome we validated the ability of the clinically available urine biomarker, IgG, to predict the risk of kidney disease progression and the beneficial effect of immunosuppression with steroids and cyclophosphamide. The fractional excretion of IgG (FE-IgG) and α1-microglobulin (FE-α1m), urine albumin/creatinine ratio, and eGFR were measured at the time of kidney biopsy. Primary outcome was progression to end stage kidney failure or kidney function (eGFR) decline ≥ 50% of baseline. Patients were followed up for 7.2 ± 4.1 years (range 1–16.8).
Results
High FE-IgG (≥0.02) predicted an increased risk of kidney failure (Hazard Ratio, (HR) 8.2, 95%CI 1.0–66.3, p = 0.048) and lower chance of remission (HR 0.18, 95%CI 0.09–0.38, p < 0.001). The ten-year cumulative risk of kidney failure was 51.7% for patients with high FE-IgG compared to only 6.2% for patients with low FE-IgG. During the study, only 24% of patients with high FE-IgG entered remission compared to 90% of patients with low FE-IgG. Combined treatment with steroids and cyclophosphamide decreased the progression rate (–40%) and increased the remission rate (+36%) only in patients with high FE-IgG.
Conclusion
In idiopathic membranous nephropathy patients with nephrotic syndrome, FE-IgG could be useful for predicting kidney disease progression, remission, and response to treatment.
【 授权许可】
2014 Bazzi et al.; licensee BioMed Central Ltd.
【 预 览 】
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20141224174554137.pdf | 527KB | download | |
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Figure 1. | 20KB | Image | download |
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【 参考文献 】
- [1]Haas M, Meehan SM, Karrison TG, Spargo BH: Changing etiologies of unexplained adult nephrotic syndrome: a comparison of renal biopsy findings from 1976-1979 and 1995-1997. Am J Kidney Dis 1997, 30(5):621-631.
- [2]Ordonez JD, Hiatt RA, Killebrew EJ, Fireman BH: The increased risk of coronary heart disease associated with nephrotic syndrome. Kidney Int 1993, 44(3):638-642.
- [3]Beck LH Jr, Bonegio RG, Lambeau G, Beck DM, Powell DW, Cummins TD, Klein JB, Salant DJ: M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med 2009, 361(1):11-21.
- [4]Ponticelli C, Altieri P, Scolari F, Passerini P, Roccatello D, Cesana B, Melis P, Valzorio B, Sasdelli M, Pasquali S, Pozzi C, Piccoli G, Lupo A, Segagni S, Antonucci F, Dugo M, Minari M, Scalia A, Pedrini L, Pisano G, Grassi C, Farina M, Bellazzi R: A randomized study comparing methylprednisolone plus chlorambucil versus methylprednisolone plus cyclophosphamide in idiopathic membranous nephropathy. J Am Soc Nephrol 1998, 9(3):444-450.
- [5]Ponticelli C, Zucchelli P, Passerini P, Cesana B, Locatelli F, Pasquali S, Sasdelli M, Redaelli B, Grassi C, Pozzi C, Bizzarri D, Banfi G: A 10-year follow-up of a randomized study with methylprednisolone and chlorambucil in membranous nephropathy. Kidney Int 1995, 48(5):1600-1604.
- [6]Schieppati A, Mosconi L, Perna A, Mecca G, Bertani T, Garattini S, Remuzzi G: Prognosis of untreated patients with idiopathic membranous nephropathy. N Engl J Med 1993, 329(2):85-89.
- [7]Schieppati A, Ruggenenti P, Perna A, Remuzzi G: Nonimmunosuppressive therapy of membranous nephropathy. Semin Nephrol 2003, 23(4):333-339.
- [8]Branten AJ, Reichert LJ, Koene RA, Wetzels JF: Oral cyclophosphamide versus chlorambucil in the treatment of patients with membranous nephropathy and renal insufficiency. QJM 1998, 91(5):359-366.
- [9]du Buf-Vereijken PW, Branten AJ, Wetzels JF, Membranous Nephropathy Study G: Cytotoxic therapy for membranous nephropathy and renal insufficiency: improved renal survival but high relapse rate. Nephrol Dial Transplant 2004, 19(5):1142-1148.
- [10]Glassock RJ: The treatment of idiopathic membranous nephropathy: a dilemma or a conundrum? Am J Kidney Dis 2004, 44(3):562-566.
- [11]Cattran D: Management of membranous nephropathy: when and what for treatment. J Am Soc Nephrol 2005, 16(5):1188-1194.
- [12]Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J, CKD-EPI (Chronic Kidney Disease Epidemiology Collab: A new equation to estimate glomerular filtration rate. Ann Intern Med 2009, 150(9):604-612.
- [13]Tofik R, Aziz R, Reda A, Rippe B, Bakoush O: The value of IgG-uria in predicting renal failure in idiopathic glomerular diseases. A long-term follow-up study. Scand J Clin Lab Invest 2011, 71(2):123-128.
- [14]Tofik R, Torffvit O, Rippe B, Bakoush O: Urine IgM-excretion as a prognostic marker for progression of type 2 diabetic nephropathy. Diabetes Res Clin Pract 2012, 95(1):139-144.
- [15]Bazzi C, Petrini C, Rizza V, Arrigo G, Beltrame A, Pisano L, D’Amico G: Urinary excretion of IgG and alpha(1)-microglobulin predicts clinical course better than extent of proteinuria in membranous nephropathy. Am J Kidney Dis 2001, 38(2):240-248.
- [16]Bazzi C, Petrini C, Rizza V, Napodano P, Paparella M, Arrigo G, Pisano L, D’Amico G: Fractional excretion of IgG predicts renal outcome and response to therapy in primary focal segmental glomerulosclerosis: a pilot study. Am J Kidney Dis 2003, 41(2):328-335.
- [17]Branten AJ, du Buf-Vereijken PW, Klasen IS, Bosch FH, Feith GW, Hollander DA, Wetzels JF: Urinary excretion of beta2-microglobulin and IgG predict prognosis in idiopathic membranous nephropathy: a validation study. J Am Soc Nephrol 2005, 16(1):169-174.
- [18]Irazabal MV, Eirin A, Lieske J, Beck LH, Sethi S, Borland TM, Dillon JJ, Nachman PH, Nasr SH, Cornell LD, Leung N, Cattran DC, Fervenza FC: Low- and high-molecular-weight urinary proteins as predictors of response to rituximab in patients with membranous nephropathy: a prospective study. Nephrol Dial Transplant 2013, 28(1):137-146.
- [19]Tofik R, Ohlsson S, Bakoush O: Urinary concentration of monocyte chemoattractant protein-1 in idiopathic glomerulonephritis: a long-term follow-up study. PLoS One 2014, 9(1):e87857.
- [20]Wasserstein AG: The more things change. Am J Kidney Dis 2001, 38(2):406-408.
- [21]Perna A, Schieppati A, Zamora J, Giuliano GA, Braun N, Remuzzi G: Immunosuppressive treatment for idiopathic membranous nephropathy: a systematic review. Am J Kidney Dis 2004, 44(3):385-401.
- [22]Bakoush O, Torffvit O, Rippe B, Tencer J: Renal function in proteinuric glomerular diseases correlates to the changes in urine IgM excretion but not to the changes in the degree of albuminuria. Clin Nephrol 2003, 59(5):345-352.
- [23]Bakoush O, Grubb A, Rippe B, Tencer J: Urine excretion of protein HC in proteinuric glomerular diseases correlates to urine IgG but not to albuminuria. Kidney Int 2001, 60(5):1904-1909.
- [24]Dussol B, Morange S, Burtey S, Indreies M, Cassuto E, Mourad G, Villar E, Pouteil-Noble C, Karaaslan H, Sichez H, Lasseur C, Delmas Y, Nogier MB, Fathallah M, Loundou A, Mayor V, Berland Y: Mycophenolate mofetil monotherapy in membranous nephropathy: a 1-year randomized controlled trial. Am J Kidney Dis 2008, 52(4):699-705.
- [25]Praga M, Barrio V, Juarez GF, Luno J, Grupo Espanol de Estudio de la Nefropatia M: Tacrolimus monotherapy in membranous nephropathy: a randomized controlled trial. Kidney Int 2007, 71(9):924-930.
- [26]Ruggenenti P, Cravedi P, Sghirlanzoni MC, Gagliardini E, Conti S, Gaspari F, Marchetti G, Abbate M, Remuzzi G: Effects of rituximab on morphofunctional abnormalities of membranous glomerulopathy. Clin J Am Soc Nephrol 2008, 3(6):1652-1659.
- [27]Berg AL, Nilsson-Ehle P, Arnadottir M: Beneficial effects of ACTH on the serum lipoprotein profile and glomerular function in patients with membranous nephropathy. Kidney Int 1999, 56(4):1534-1543.
- [28]Ruggenenti P, Cravedi P, Chianca A, Perna A, Ruggiero B, Gaspari F, Rambaldi A, Marasa M, Remuzzi G: Rituximab in idiopathic membranous nephropathy. J Am Soc Nephrol 2012, 23(8):1416-1425.