Skip to main content
Download PDF

Fractional excretion of IgG in idiopathic membranous nephropathy with nephrotic syndrome: a predictive marker of risk and drug responsiveness

BMC Nephrology volume 15, Article number: 74 (2014) Cite this article

Abstract

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.

Peer Review reports

Background

Idiopathic membranous nephropathy (IMN) is a major cause of nephrotic syndrome (NS) in adult patients [1]. NS is associated with an increased risk of kidney failure and death from cardiovascular causes [2]. IMN is characterised by subepithelial localisation of IgG immune-complexes and lack of significant proliferation in the glomerular tuft. The recent discovery of the podocyte antigen PLA2R and its corresponding IgG autoantibodies confirmed the autoimmune nature of the disease [3].

There is no specific treatment for IMN. Early initiation of immunosuppressive treatment with steroids and cyclophosphamide has been recommended by some investigators [4, 5]. Because of the high rate of spontaneous remission (about 30%), others suggested an initial conservative approach [6, 7]. Immunosuppressive treatment could be harmful, but waiting until the condition starts to progress carries the risk of missing the “window of opportunity” for treatment [8–10]. Once this assessment is made, an individualised treatment based on risk versus benefit of the immunosuppressive treatment can be advocated [11].

Nowadays, the severity of kidney disease is commonly staged according to the kidney function estimated from serum creatinine (eGFR) [12]. However, eGFR is not an early predictive marker for treatment decisions [9]. Therefore, the search continues for early predictive markers that can estimate the risk of kidney disease progression. The ideal prognostic biomarker should be accurate and easy to implement in clinical practice. Such a biomarker could guide clinical decisions to avoid unnecessary treatment of patients who are not at risk of progression and to avoid unnecessary delay in initiation of treatment for those at high risk of progression to kidney failure.

As in other types of glomerular diseases, the primary main lesion in IMN is alteration of the glomerular filtration barrier (GFB) function with increased excretion of albumin (molecular radius, r =36 Å) and high molecular weight proteins such as IgG (r = 55 Å) and IgM (r = 120 Å) [13, 14]. Thus, increased urine IgG concentrations in nephrotic patients could reflect activity and severity of the glomerulonephritis [13, 15, 16]. Recent studies have shown that IgG-uria could provide early prognostic information for patients with glomerular disease [13, 15, 17, 18]. However, its value in predicting the remission and treatment outcome is still unclear. Using the data from the Milano and Lund glomerulonephritis longitudinal cohorts, we assessed whether IgG-uria can predict the functional outcome (remission versus progression) in patients with IMN and NS. We also evaluated the ability of IgG-uria to identify patients who might benefit from immunosuppressive treatment.

Methods

Patients

The cohort was derived from patients with IMN and NS diagnosed between January 1992 and December 2005 at the Nephrology Unit of San Carlo Borromeo Hospital, Milan, Italy (n = 70) and the Nephrology Department of Lund University, Sweden (n = 16). The inclusion criteria were nephrotic range proteinuria (24-hour proteinuria ≥ 3.5 g, or urinary albumin/creatinine ratio ≥ 2.0 g/g); serum albumin < 3.0 g/dL; baseline sCr <2.7 mg/dL and eGFR ≥24 ml/min/1.73 m2). The morphological diagnosis was in all cases established by light microscopy and immunofluorescence staining of representative kidney biopsy specimens containing at least six glomeruli. One histo-pathologist in each study center scored semi-quantitativly the tubulo-interstitial fibrosis as normal interstitium, focal or diffuse tubule-interstitial fibrosis, and the percentage of global glomerulosclerosis (GGS) was calculated. The patients did not have clinical or laboratory signs of secondary causes of IMN, such as systemic lupus erythematosus, connective tissue diseases, cancer, or medication with gold or penicillamine. The collection of 24-hour urine was done the day before the kidney biopsy, and the blood samples and the second voided urine specimens were obtained in the morning of the day of renal biopsy. The study complied with the Declaration of Helsinki and the local requirements for ethical approval (Lund regional ethical committee: LU 47-02). All patients gave informed written consent. The baseline characteristics of the cohort are in Table 1.

Table 1 Baseline characteristics of patients with idiopathic membranous nephropathy and nephrotic syndrome, classified according to fractional excretion of IgG
Full size table

Treatment and follow-up

Thirty-five patients were treated only with supportive therapy, such as diuretics, antihypertensives, angiotensin enzyme inhibitors (ACEi/ARBs), statins, anti-platelet agents, and vitamin D3. Thirty-seven patients, besides supportive therapy, were treated soon after diagnosis with steroids and cyclophosphamide (St + Cyc) for six months according to the Ponticelli protocol: methylprednisolone 0.5–1.0 g iv for 3 days at the beginning of months 1, 3 and 5, followed by oral prednisolone 0.5 mg/kg/day during months 1, 3 and 5, and cyclophosphamide 1–2 mg/kg/day during months 2, 4 and 6 (lower dose of both drugs for elderly patients and patients with low GFR) [4]. Twelve patients were treated with steroids alone: five with prednisone 1 mg/kg/day for 4–12 months, and seven with ACTH 1–2 mg weekly for 4–11 months. Patients were followed up until the last planned clinic visit in 2009. The primary outcome was progression to kidney failure defined as start of renal replacement therapy (ESRD) or reduction of eGFR by ≥ 50% of baseline. The secondary outcome was complete or partial remission of NS (proteinuria < 0.2 or < 2.0 g/day, respectively).

Laboratory analysis

A blood sample and a second morning fresh urine sample were analysed for concentration of creatinine, albumin, IgG and alpha 1 microglobulin in the chemistry laboratory of Azienda Ospedaliera Ospedale San Carlo Borromeo, Milan, and in the chemistry laboratory of hospital of Lund. Serum creatinine (sCr) and urinary creatinine (uCr) were measured enzymatically and expressed in μmol/L. Serum and urinary IgG, albumin and α1-microglobulin (α1m) were measured by immunonephelometry method on a BNA nephelometer (Behring, Milan, Italy) using rabbit serum antihuman antibodies (Behring) [16], and by immunoturbidimetry using a Cobas Mira S system (Roche Inc.) [19].

Calculations

Urinary albumin-to-creatinine ratio (mg/g) (ACR) is the ratio of urinary albumin (mg/L) to urinary creatinine (g/L); fractional excretion of IgG (FE-IgG) and α1m (FE-α1m), expressed per 100 ml of creatinine clearance, was calculated according to the formula FE-IgG = (urinary protein/serum protein) × (serum creatinine/urinary creatinine) × 100.

Glomerular filtration rate (eGFR) was estimated from serum creatinine using the Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) formula [12].

Statistical analysis

All statistical analyses were performed using IBM SPSS software version 19.0. Data are expressed as means ± SD. The differences between the study groups were determined using the Mann-Whitney U test, or the unpaired t-test as appropriate. Proportions were compared by Chi-square analysis. Correlations were assessed with Spearman Rank test. Receiver Operating Characteristic (ROC) curve was used to determine the cut-off values for the predictors of kidney failure (Table 2). These cut-off values were applied to the patients to create two groups for each predictor - high risk and low risk. Patients were also divided into high and low eGFR groups using a cut-off of < 60 ml/min/1.73 m2 according to the K/DOQI guidelines. eGFR < 60 ml/min/1.73 m2 identifies patients with moderate to severe CKD. The sensitivity and specificity of these cut-off points were used to calculate the positive likelihood ratio (Table 2). Kidney survival analysis was performed using the Kaplan–Meier method. Survival time was calculated from the date of diagnosis. The time horizon for cumulative kidney survival rate was set at 10 years. Patients were censored at the time of death or at the end of follow-up. Patients with missing data were excluded (2 patients was missing alpha 1 microglobulin ). Log-rank test was used to assess the difference in survival. Univariate and multivariate Cox proportional hazards regression analysis was performed on the population as a whole and on the relevant treatment groups. The tested dependent variables were FE-IgG, FE-α1m, ACR and eGFR. Two-sided p <0.05 was considered statistically significant.

Table 2 Characteristics of receiver operating curves (ROC) for the investigated biomarkers: area under the curves (AUC), cut-off levels, sensitivity, specificity and likelihood ratio for predicting kidney failure (n 84) and No remission (n 70) in idiopathic membranous nephropathy patients with nephrotic syndrome
Full size table

Results

The fractional excretion of IgG (FE-IgG) was measured in 84 (34 female) patients Table 1. The overall average follow-up time was 86 ± 50 months (range 12–202). During follow-up, 20 patients progressed to kidney failure, 14 patients to ESRD, and 6 patients to eGFR ≤50% of baseline.

FE-IgG was strongly related to the baseline eGFR (r: –0.654, p = 0.01) and last eGFR (r: –0.570, p = 0.01), and weakly with global glomerulosclerosis (r = 0.380, p = 0.001) and tubulo-interstitial fibrosis (r = 0.297, p = 0.01). The optimal cut-off level for high FE-IgG was ≥ 0.02, for high FE-α1m ≥ 0.24, and for high ACR ≥ 4000 mg/g uCr (Table 2). FE-IgG had a better likelihood ratio for prediction of kidney failure thanFE-α1m, ACR or eGFR (Table 2).

The results of univariate Cox-regression analysis are shown in Table 3. In a multivariate Cox-regression analysis the association between FE-IgG and progression to kidney failure remains highly significant even after adjustment for the key potential confounding factors: age, kidney function, blood pressure, proteinuria, and treatment with ACEi/ARB and immunosuppression drugs, (HR 20.84, 95% CI: 2.8–156.8, p =0.003, Figure 1).

Table 3 Univariate Cox regression analysis for outcome of renal failure in 84 patients with idiopathic membranous nephropathy and nephrotic syndrome
Full size table
Figure 1
figure 1

Kidney survival in patients with idiopathic membranous nephropathy and nephrotic syndrome according to FE-IgG levels.

Full size image

Remission of nephrotic syndrome (NS)

Remission rate could be evaluated only for Milano group of patients (n = 70) (Figure 2). Irrespective of immunosuppressive treatment, most patients who had low FE-IgG went into remission (89.7% of patients at 36 months, 95% CI: 21–51). In contrast, the remission occurred only in less than a third of patients with high FE-IgG and at a later time (24.4% of patients at 128 months, 95% CI: 105–151, p <0.001).

Figure 2
figure 2

Remission of proteinuria in patients with idiopathic membranous nephropathy and nephrotic syndrome according to FE-IgG level.

Full size image

FE-α1m groups

The remission was more frequent and earlier in patients with low FE-α1m (82.8% of patients at 47.1 months, 95%CI: 27–67 months) than patients with high FE-α1m (29.3%, at 119.9 months, 95% CI: 96–144, p <0.001).

ACR groups

The remission was more frequent and earlier in patients with low ACR (75.8% of pats, at 55.1 months, 95% CI: 33–77), than patients with high ACR (29.7%, at 109.5 months, 95% CI: 86–133, p < 0.001).

eGFR groups

Most of the patients with baseline eGFR ≥ 60 ml/min/1.73 m2 went into remission (69.6%, at 60.3 months, 95% CI: 41–79) compared to patients with baseline eGFR < 60 ml/min/1.73 m2 (16.7%, at 142.7 months, 95% CI: 118–167, p <0.001).

The multivariate Cox regression analysis identified only FE-IgG as an independent predictor for remission (HR 0.18, 95% CI, 0.09-0.38, p <0.001) (Figure 2).

IgG fractional excretion and response to treatment

The 37 patients treated with steroids and cyclophosphamide were compared with the 35 patients treated only with supportive therapy. The baseline characteristics of the two groups are in Table 4. There was no difference in initial kidney function or degree of proteinuria. During the study, the overall rates of progression to kidney failure in the untreated and treated patients did not differ significantly (37% vs. 27.6%, respectively, p = 0.84). However, untreated patients with high FE-IgG were more likely than treated patients to progress to kidney failure (72% vs. 43%, respectively, p =0.014) (Figure 3a). For patients with low FE-IgG there was no significant difference in risk of progression to kidney failure between the untreated and treated patients (12.5% and 0%, respectively, p = 0.39) (Figure 3b).

Table 4 Clinical, proteinuric and histologic parameters of 35 idiopathic membranous nephropathy patients with nephrotic syndrome not treated with immunosuppressive drugs and 37 others treated with combined steroids and cyclophosphamide
Full size table
Figure 3
figure 3

Effect of immunosuppressive treatment on kidney survival in patients with idiopathic membranous nephropathy and nephrotic syndrome, according to FE-IgG level. a: untreated patients with high FE-IgG were more likely than treated patients to progress to kidney failure. b: patients with low FE-IgG behaved similarly, progressing slowly to kidney failure.

Full size image

Untreated and treated patient did not differ in overall remission rate (51.7% vs. 51.2%, p = 0.7). However, for patients with high FE-IgG, the remission rate was 0% for untreated and 36% for treated patients (p = 0.025). There was no difference in the frequency of remission between untreated and treated patients with low FE-IgG (93.7% vs. 84.6%, p = 0.23).

Discussion

This longitudinal cohort study validated the predictive value of the fractional excretion of IgG in IMN patients with nephrotic syndrome. The heterogeneity of the progression to kidney failure in IMN patients and the lack of a reliable marker of disease severity has been a major confounding factor that contributed significantly to the contradictory results of the previous clinical treatment trials [20]. A recent meta-analysis of 1025 patients enrolled in 18 random controlled trials showed an increase in the likelihood of remission for patients treated with steroids and alkylating agents, but there were no beneficial effects on kidney function [21]. In our cohort, immunosuppressive treatment with steroids and cyclophosphamide significantly improved the clinical outcome only in patients with increased urinary excretion of IgG (FE-IgG ≥ 0.02). For these patients, immunosuppressive treatment reduced the 10-year incidence of kidney failure by 40% and increased the remission rate by 36%. Patients with lower concentrations of urine IgG (FE-IgG <0.020) went into spontaneous remission more frequently and maintained kidney function even without immunosuppressive treatment.

As in previous studies, our cohort showed that impairment of kidney function and increased proteinuria are associated with faster progression to kidney failure. However, the fractional excretion of IgG predicts both remission of NS (HR 0.18) and progression to kidney failure (HR 8.2) independently from albuminuria and GFR.

The role of albuminuria in the progression of kidney disease has been questioned in many experimental and clinical studies. The GFR estimated from serum creatinine is considered a late sign of the severity of kidney disease [22, 23]. Thus, inclusion of FE-IgG in clinical practice guidelines may provide a substantial improvement in risk prediction during the early stages of IMN. It might help clinicians to individualise treatment and thereby improve outcome. Patients with high FE-IgG may benefit from more intensive monitoring of kidney function and from early initiation of immunosuppressive therapy.

The last few years have seen the development of various new immunosuppressive treatments, such as mycophenolate mophetil, tacrolimus, rituximab, and synthetic ACTH for patients not responding to steroids and alkylating agents [24–28]. It will be of clinical interest to include FE-IgG in future treatment trials.

The main strength of our study, the possibility of using a simple, practical renal biomarker that can be included in routine clinical care for kidney disease patients, is particularly relevant. Urine IgG measured in a spot urine sample and calculation of FE-IgG can be integrated into the routine laboratory investigation in most clinical laboratories. Nephrotic patients are usually managed by kidney specialist, and the results of this study can be generalised among different health care systems.

Calculating the risk of kidney failure in nephrotic patients is important for management decisions, and maintaining kidney function is usually associated with better survival. Whether immunosuppressive treatment improves patient survival should be addressed in multicentre longitudinal studies on large numbers of patients.

Conclusions

In conclusion, in idiopathic membranous nephropathy patients with nephrotic syndrome, urinary excretion of IgG could be helpful, in addition to albuminuria, for assessment of the risk of disease progression and response to treatment. Validation of our results on a large external cohort and in new clinical trials is warranted.

References

  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. 10.1016/S0272-6386(97)90485-6.

    Article  CAS  PubMed  Google Scholar 

  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. 10.1038/ki.1993.292.

    Article  CAS  PubMed  Google Scholar 

  3. Beck LH, 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. 10.1056/NEJMoa0810457.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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. 10.1038/ki.1995.453.

    Article  CAS  PubMed  Google Scholar 

  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. 10.1056/NEJM199307083290203.

    Article  CAS  PubMed  Google Scholar 

  7. Schieppati A, Ruggenenti P, Perna A, Remuzzi G: Nonimmunosuppressive therapy of membranous nephropathy. Semin Nephrol. 2003, 23 (4): 333-339. 10.1016/S0270-9295(03)00050-0.

    Article  CAS  PubMed  Google Scholar 

  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. 10.1093/qjmed/91.5.359.

    Article  CAS  PubMed  Google Scholar 

  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. 10.1093/ndt/gfh036.

    Article  CAS  PubMed  Google Scholar 

  10. Glassock RJ: The treatment of idiopathic membranous nephropathy: a dilemma or a conundrum?. Am J Kidney Dis. 2004, 44 (3): 562-566. 10.1053/j.ajkd.2004.06.003.

    Article  PubMed  Google Scholar 

  11. Cattran D: Management of membranous nephropathy: when and what for treatment. J Am Soc Nephrol. 2005, 16 (5): 1188-1194. 10.1681/ASN.2005010028.

    Article  PubMed  Google Scholar 

  12. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, 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. 10.7326/0003-4819-150-9-200905050-00006.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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. 10.1016/j.diabres.2011.10.008.

    Article  CAS  PubMed  Google Scholar 

  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. 10.1053/ajkd.2001.26080.

    Article  CAS  PubMed  Google Scholar 

  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. 10.1053/ajkd.2003.50040.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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. 10.1093/ndt/gfs379.

    Article  CAS  PubMed  Google Scholar 

  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): e87857-10.1371/journal.pone.0087857.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Wasserstein AG: The more things change. Am J Kidney Dis. 2001, 38 (2): 406-408. 10.1053/ajkd.2001.27007.

    Article  CAS  PubMed  Google Scholar 

  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. 10.1053/j.ajkd.2004.05.020.

    Article  PubMed  Google Scholar 

  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. 10.5414/CNP59345.

    Article  CAS  PubMed  Google Scholar 

  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. 10.1046/j.1523-1755.2001.00018.x.

    Article  CAS  PubMed  Google Scholar 

  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. 10.1053/j.ajkd.2008.04.013.

    Article  CAS  PubMed  Google Scholar 

  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. 10.1038/sj.ki.5002215.

    Article  CAS  PubMed  Google Scholar 

  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. 10.2215/CJN.01730408.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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. 10.1046/j.1523-1755.1999.00675.x.

    Article  CAS  PubMed  Google Scholar 

  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. 10.1681/ASN.2012020181.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Pre-publication history

Download references

Acknowledgements

We wish to thank Dr. Jawad Hashim, Department of Family Medicine, UAE University, for critical review of the statistical analysis, and Dr. Amin Bredan, for writing assistance.

Author information

Authors and Affiliations

  1. D’Amico Foundation for Renal Diseases Research, Milan, Italy

    Claudio Bazzi & Giuseppe D’Amico

  2. Biochemical Laboratoryt, Azienda Ospedaliera Ospedale San Carlo Borromeo, Milan, Italy

    Virginia Rizza

  3. Department of Nephrology, Lund University, Lund, Sweden

    Rafid Tofik, Anna-Lena Berg & Omran Bakoush

  4. Nephrology and Dialysis Unit, Azienda Ospedaliera Ospedale San Carlo Borromeo, Milan, Italy

    Daniela Casellato & Maurizio Gallieni

  5. Department of Internal Medicine, UAE University, Al Ain, United Arab Emirates

    Omran Bakoush

Authors
  1. Claudio Bazzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Virginia Rizza
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daniela Casellato
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rafid Tofik
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anna-Lena Berg
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Maurizio Gallieni
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Giuseppe D’Amico
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Omran Bakoush
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Omran Bakoush.

Additional information

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

CB and OB designed the study, analyzed the data, and draft the manuscript. VR, DC, RT, AB, MG, and GD contributed to the design of the study and drafting the manuscript. All authors read and approved the final manuscript.

Authors’ original submitted files for images

Below are the links to the authors’ original submitted files for images.

Authors’ original file for figure 1

Authors’ original file for figure 2

Authors’ original file for figure 3

Rights and permissions

Open Access  This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.

The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/.

The Creative Commons Public Domain Dedication waiver (https://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bazzi, C., Rizza, V., Casellato, D. et al. Fractional excretion of IgG in idiopathic membranous nephropathy with nephrotic syndrome: a predictive marker of risk and drug responsiveness. BMC Nephrol 15, 74 (2014). https://doi.org/10.1186/1471-2369-15-74

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/1471-2369-15-74

Keywords

BMC Nephrology

ISSN: 1471-2369

Contact us