Article

IgA Nephropathy with

Leal C. Herlitz,* Andrew S. Bomback,† Michael B. Stokes,* Jai Radhakrishnan,† Vivette D. D’Agati,* and Glen S. Markowitz*

Abstract Background and objectives Patients with IgA nephropathy typically present with and subnephrotic . is uncommon in IgA nephropathy, and when present, it is usually associated with severe histologic features, such as endocapillary proliferation, segmental sclerosis, and crescent formation. Rarely, patients with IgA nephropathy present with nephrotic syndrome and only mild mesangial disease. This *Department of Pathology and Cell study sought to better characterize these patients. Biology, Division of Renal Pathology, and Design, setting, participants, & measurements A retrospective review of cases of IgA nephropathy diagnosed †Department of from 2004 to 2011 identified patients with nephrotic range proteinuria and histologically mild IgA nephropathy. Medicine, Division of fi fi fi , Speci cally, using the Oxford Classi cation of IgA Nephropathy, we identi ed cases that lacked endocapillary Columbia University proliferation or segmental sclerosis. Medical Center and the New York Results The cohort consisted of 17 patients, including 10 men and 15 adults. The median serum was Presbyterian Hospital, New York, New York 0.9 mg/dl (range=0.7–3.1), median 24-hour urine was 8.0 g/d (3.0–18.0 g), and 14 patients were fully fi nephrotic, whereas the remaining 3 patients ful lled two of three criteria for nephrotic syndrome. Biopsies Correspondence: revealed IgA-dominant or codominant deposits accompanied by mesangial proliferation in 14 patients (82.4%). Dr. Leal C. Herlitz, Electron showed mesangial deposits and extensive foot process effacement (median=90%). Initial Department of treatment consisted of corticosteroids, although many patients required additional agents to maintain remission Pathology, 630 West status. Over a median follow-up of 20 months (2.2–82 months), 14 patients experienced a complete response, 168th Street, VC14- – 238, New York, NY and 3 patients showed a partial response, with a median response time of 2 months (0.5 27 months). At least 10032. Email: one relapse of nephrotic syndrome occurred in nine patients (53%). All patients exhibited stable or improved [email protected] renal function over the follow-up period.

Conclusions The findings in this cohort and previous studies suggest that rare cases of mild IgA nephropathy with nephrotic range proteinuria exhibit a clinical presentation, biopsy findings, treatment response, and outcome more typical of IgA nephropathy with superimposed minimal change disease. This study favors the view that such cases represent a dual . Clin J Am Soc Nephrol 9: 1033–1039, 2014. doi: 10.2215/CJN.11951113

Introduction proliferative IgAN. In these patients, electron micros- IgA nephropathy (IgAN) is the most common GN copy typically reveals diffuse foot process effacement worldwide (1). IgAN is typically an indolent disease without peripheral capillary wall immune deposits, with a slow progression to end stage disease reminiscent of minimal change disease (MCD). Many in approximately 30% of patients over 20 years (2). of the patients are rapidly responsive to treatment Clinical risk factors for progression of IgAN include with corticosteroids. Such cases are uncommon but proteinuria.1.0 g/d, , and persistent have been presented as case reports and in small series microscopic hematuria (1). Clinical presentations of over the last 30 years (4–17). Some of these reports IgAN vary widely, but the most common presenta- have suggested that the clinical and pathologic find- tion is that of hematuria with subnephrotic protein- ings in these unusual cases of IgAN (4–17), as well as uria. Nephrotic syndrome (NS) is an unusual the clinical outcomes (4–17), are more typical of mild presentation occurring in approximately 5% of cases IgAN with superimposed MCD. (3). Heavy proteinuria and/or NS in patients with The literature on treating MCD and IgAN as separate IgAN are often accompanied by renal insufficiency entities is abundant. In recent years, first-line treatment and biopsy findings of more aggressive disease, of MCD (i.e., corticosteroids) (18) also has been estab- with endocapillary proliferative and sclerosing glo- lished as a standard therapy for patients with IgAN merular lesions typically associated with subendothe- with significant proteinuria (19–21), generally consid- lial IgA deposits. ered to be .1 g/d despite effective use of renin angio- A subset of patients with IgAN presents with NS tensin system-blocking drugs. Thus, the patient who and has histologic findings of only mild mesangial presents with NS and is found to have findings www.cjasn.org Vol 9 June, 2014 Copyright © 2014 by the American Society of Nephrology 1033 1034 Clinical Journal of the American Society of Nephrology

suggestive of both MCD and mild IgAN should be a straight- urinary sediment. NS was defined as NRP, hypoalbumin- forward treatment decision. Still, the prognosis for these pa- emia, and peripheral . Hypertension was defined as tients remain uncertain (specifically, whether they will have systolic BP.140 mmHg, diastolic BP.90 mmHg, or use of the often benign long-term course of mild IgAN or the fre- antihypertension medication. For children, NRP was defined quently relapse-ridden course of MCD). as .40 mg/m2 per hour (24), was defined We present a series of 17 patients from the United States as serum albumin,2.5 g/dl (24), renal insufficiency was de- who developed nephrotic range proteinuria (NRP) and, in fined as calculated creatinine clearance,90 ml/min normal- most cases, full NS and were found to have mild mesangial ized for body surface area (25), and hypertension was based proliferative IgAN with diffuse foot process on the clinical assessment of the referring nephrologist. effacement. The mild degree of immune complex deposi- For the purpose of outcomes analysis, the following tion and mesangial proliferation, in the absence of endo- definitions were applied. Stable renal function was defined capillary proliferation or subendothelial deposits, seemed as a change in SCr of #25% of the initial value. Complete insufficient to explain the severe foot process effacement. remission (CR) was 24-hour urine protein of #500 mg/d at We believe that these cases represent mild IgAN with last follow-up. Partial remission (PR) was 24-hour urine pro- superimposed podocytopathy, which is most consistent tein of #3 g/d and a reduction in proteinuria of at least 50%. with MCD. Clinical presentation, biopsy findings, treat- CRs were further subdivided into patients who achieved re- ment, and prolonged follow-up are presented to better mission but were still on therapy at the last follow-up (CR characterize these unusual cases of mild IgAN with severe on therapy) and patients in remission who were no longer proteinuria. on therapy (CR off therapy). If a patient achieved remission for 6 months or longer while off therapy, subsequent epi- sodes of NS were considered to be relapses. If remission Materials and Methods status was lost within 6 months of therapy withdrawal, All native renal biopsies received and processed at the return of proteinuria was considered to be evidence of Columbia University Medical Center from 2004 to 2011 therapy dependence and not categorized as a relapse. Data were reviewed retrospectively (Columbia University In- are presented descriptively, because the small number of stitutional Review Board AAAI3051) for the diagnosis of subjects precludes formal statistical analysis. IgAN occurring in the setting of NS or NRP with edema or hypoalbuminemia. IgAN was defined by the presence of dominant or codominant glomerular staining for IgA in the Results absence of systemic . Biopsies were graded according The cohort of 17 patients included 10 men and 7 women: 15 to the Oxford Classification of IgAN (22,23). Specifically, adults between the ages of 22 and 72 years and 2 children the degree of mesangial hypercellularity (M), the presence (ages 5 and 6 years). Eleven patients were Caucasian, three of endocapillary proliferation (E) and segmental glomeru- patients were Hispanic, two patients were Asian, and one losclerosis (S), and the degree of tubulointerstitial scarring patient was African American (Table 1). Past medical history (T) were assessed, producing an Oxford-MEST score. Cases was significant for obesity in four patients, diabetes in two with endocapillary proliferation, necrosis, or cellular cres- patients, and coronary artery disease and chronic obstructive cents were excluded, and an Oxford-MEST score of either pulmonary disease in one patient each. No secondary causes M1E0 or M0E0 was required. We identified a total of 17 of IgAN were identified (e.g., chronic disease, HIV in- cases, which originated from multiple nephrology centers fection, and inflammatory bowel disease). in the northeastern United States. All cases were processed Laboratory findings at the time of biopsy are summarized for light microscopy, immunofluorescence, and electron in Table 1. Fourteen patients (82.4%) had preserved renal microscopy according to standard techniques. For immu- function (SCr#1.2) at the time of biopsy. The median 24- nofluorescence, 3-mm cryostat sections were stained with hour urine protein was 8.0 g/d (range=3.0–18.0 g), and me- FITC-conjugated rabbit anti-human IgG, IgM, IgA, C3, dian serum albumin was 2.1 mg/dl (range=0.7–4.0 mg/dl), C1q, k-light chain, and l-light chain (Dako Corporation, with all but one patient having evidence of hypoalbuminemia. Carpinteria, CA). The intensity of immunofluorescence Peripheral edema was present in 15 patients. Fourteen pa- positivity was graded on a scale of 0, trace, or 1–3+. Electron tients fulfilled criteria for full NS, and the remaining three microscopy was performed with a JEOL 1011 electron mi- patients had NRP. Of the three patients not qualifying as croscope. For each case, a percentage estimate of the degree fully nephrotic, two patients lacked only edema, and one pa- of podocyte foot process effacement was performed by an tient had edema but a serum albumin of 4.0 mg/dl. Serologic experienced renal pathologist examining at least 10 distinct testing revealed positive anti-nuclear in two pa- fields. tients, neither of whom had other clinical or laboratory features Patient charts were reviewed retrospectively for presenting of systemic lupus. Complement levels (C3, C4, and CH50) symptoms, laboratory findings, treatment, and follow-up. were normal in all patients. For the purpose of establishing clinical definitions, pa- The renal biopsy findings are presented in Table 2. Glo- tients$18 years of age were considered adults (n=15) and merular findings by light microscopy were predominantly those patients,18 years of age were considered children mild (Figure 1A). There was mesangial proliferation (Oxford (n=2). For adults, the following definitions were used: M1) in 14 biopsies (82.4%), whereas the remaining 3 biopsies NRP: 24-hour urine protein$3 g/d; hypoalbuminemia: se- (17.6%) had no significant mesangial proliferation (Oxford rum albumin#3.5 g/dl; renal insufficiency: serum creatinine M0). Based on inclusion criteria, none of the biopsies exhibit- (SCr).1.2 mg/dl; and hematuria: more than five red blood ed endocapillary proliferation (Oxford E0), necrosis, or cel- cells per high-power field on microscopic examination of the lular crescents. One biopsy had a single segmental scar Clin J Am Soc Nephrol 9: 1033–1039, June, 2014 IgAN with Minimal Change Disease, Herlitz et al. 1035

Table 1. Clinical characteristics Table 2. Pathologic findings

Characteristic Value Modality/Finding Value

Age (yr), median (range) 46 (5–72) Light microscopy ,18, n 2 Number of glomeruli, 15 (5–38) 18–50, n 9 median (range) .50, n 6 Percent of globally sclerotic 5.5 (1–31) Sex (men/women), n (%) 10/7 (59/41) glomeruli, median (range) Race/ethnicity, n (%) Number of biopsies with no 3(17.6) White 11 (64.7) cellular proliferation (%) Hispanic 3 (17.6) Number of biopsies with 14 (82.4) Asian 2 (11.8) mesangial proliferation only (%) Black or African American 1 (5.9) Number of biopsies with 1(5.9) Serum creatinine (mg/dl), 0.9 (0.7–3.1) segmental sclerosis (%)a median (range) Tubulointerstitial scarring Renal insufficiency, n (%) 3 (17.6) Biopsies with ,5% scarring, n (%) 8(47.1) 24-h Urine protein (g/d), 8.0 (3–18) Biopsies with 5%–10% scarring, n (%) 9(52.9) median (range) Oxford-MEST classification of Serum albumin (g/dl), 2.1 (0.7–4) IgAN, n (%) median (range) M1, E0, S0, and T0 13 (76.4) Peripheral edema, n (%) 15 (88.2) M0, E0, S0, and T0 3(17.6) Full nephrotic syndrome, 14 (82.4) M1, E0, S1, and T0a 1(5.9) n (%)a Immunofluorescence Hematuria, n (%) 9 (52.9) Percent IgA-dominant or 100 Hypertension, n (%) 5 (29.4) codominant IgA intensity, scale 0–3+, 2(1–3) aOf three patients not meeting criteria for full nephrotic syn- median (range) drome, two patients lacked only edema. One patient had ne- Electron microscopy – phrotic range proteinuria and edema but normal serum Percent podocyte foot 90 (50 100) albumin of 4 g/dl. process effacement, median (range)b Mesangial deposits, n (%) 17 (100) Subendothelial deposits, n (%) 0 (0) Subepithelial deposits, n (%) 1 (5.9) associated with a small overlying fibrous crescent, sugges- tive of an old proliferative lesion of IgAN. This patient Oxford-MEST, the degree of mesangial hypercellularity (M), had a 10-year history of -dependent NS with stable the presence of endocapillary proliferation (E) and segmental creatinine. No other biopsy exhibited segmental sclerosis glomerulosclerosis (S), and the degree of tubulointerstitial lesions. Tubulointerstitial scarring was mild in all cases scarring (T) score; IgAN, IgA nephropathy; M1, more than 50% (Oxford T0). Using the Oxford classification for IgAN, pa- of glomeruli with at least four cells per mesangial area; E0, no tients fell into one of three MEST scores: M1, E0, S0, and T0 endocapillary proliferation; S0, no segmental glomerulo- in 13 patients (76.4%); M0, E0, S0, and T0 in 3 patients sclerosis; T0, tubulointerstitial scarring of 0%–25% of the cor- (17.6%); and M1, E0, S1, and T0 in 1 patient (5.9%) with a tical area; M0, no significant mesangial hypercellularity; S1, segmental sclerosis in at least one . 10-year history of steroid-dependent NS. a Immunofluorescence showed dominant or codominant One patient, whose clinical history was marked by 10 years of steroid-dependent nephrotic syndrome with stable renal func- IgA staining in all cases (Figure 1B), with a median intensity – – tion, had a single glomerulus with a segmental scar and over- of 2, a mean intensity of 1.85, and a range of 1 3+ (scale 0 3 fi fi lying brous crescent. +). Staining was con ned to the mesangium in all cases. bThree patients had podocyte effacement of ,70%. Two of these Electron microscopy (Figure 1, C and D) showed mesangial three patients were biopsied during a nephrotic syndrome re- immune-type electron dense deposits in all 17 cases, rare lapse and had begun steroid treatment before biopsy. The third segmental subepithelial deposits in 1 case, and no subendo- patient was taking low-dose prednisone (15 mg/d) for chronic thelial deposits in any case. No biopsy exhibited glomerular obstructive pulmonary disease. basement membrane thinning or lamellation. Podocyte foot process effacement ranged from 50% to 100%, with median effacement of 90%. Three cases showed podocyte effacement and various alternative regimens were used in patients who of ,70%. Two of these patients were biopsied during a re- did not achieve sustained response. Fourteen patients expe- lapse of NS and had already commenced corticosteroid ther- rienced CR, three patients achieved PR, and there were no apy before biopsy. The third patient was on low-dose nonresponders. The response categories were further subdi- prednisone (15 mg/d) for chronic obstructive pulmonary vided into patients who were therapy-dependent at the time disease. of last follow-up (CR on therapy, n=5; PR on therapy, n=3) Clinical follow-up is presented in Table 3 and was avail- and patients who were off therapy at last follow-up (CR off able in all 17 cases, with median and mean follow-up dura- therapy, n=9). Time to achieve response averaged 4.8 tions of 20 and 30 months, respectively (range=2.2–82 months, with a median time of 2 months and a range of months). All patients were treated initially with corticosteroids, 0.5–27 months. 1036 Clinical Journal of the American Society of Nephrology

Figure 1. | Light microscopic, immunofluorescence, and ultrastructural findings in IgA nephropathy with minimal change disease. (A) A glomerulus exhibits mesangial proliferation without evidence of endocapillary proliferation, segmental sclerosis, or crescent formation (Oxford M1, E0, and S0; hematoxylin and eosin). (B) Immunofluorescence reveals 2+ intensity staining for IgA restricted to mesangial areas. (C and D) Electron micrographs show mesangial electron dense deposits (arrows) and extensive foot process effacement. No peripheral glomerular capillary wall immune deposits are present. Original magnification, 3400 in A and B; 38000 in C; 310,000 in D. E0, no endo- capillary proliferation; M1, more than 50% of glomeruli with at least four cells per mesangial area; S0, no segmental glomerulosclerosis.

Nine patients (53%) showed a CR and were off therapy at patient received MMF only, and one patient received CSA the time of the last follow-up. Three of these patients had followed by FK506. Renal function was stable in four patients experienced at least one episode of relapsing proteinuria and improved in one patient at last follow-up. during the follow-up period and were subsequently success- Three patients achieved only a PR and were being actively fully treated with (CTX) in one patient, treated at the time of the last follow-up. Two patients have cyclosporine (CSA) followed by CTX in one patient, and never been off therapy since initial diagnosis, including one FK506 (which caused AKI) followed by CTX and 1 year of patient with a PR who remains steroid-dependent after 5 maintenance therapy with mycophenolate mofetil (MMF) in months of treatment and one patient who was treated with one patient. Renal function in the group of complete followed by MMF and has been on MMF for 10 responders off therapy at last follow-up was stable in seven months. The third patient has experienced a relapsing course patients and showed improvement in two patients. and been sequentially treated with prednisone, CSA, , Five patients achieved a CR but were still dependent on MMF, and most recently, adrenocorticotrophic hormone. therapy at the time of last follow-up. Each of these five Despite the limited response to therapy, all three patients patients had experienced at least one relapse when therapy had stable renal function at last follow-up. had been withdrawn. One patient was treated solely with steroids and remained steroid-dependent at last follow-up, Discussion whereas another patient briefly received , which In patients with IgAN, there is typically a reasonable produced leucopenia, and was switched back to steroids. The degree of correlation between clinical and pathologic remaining three patients were treated with alternative findings. When solely mesangial proliferation is present, regimens after steroids had failed, and they continued to patients most commonly exhibit subnephrotic proteinuria, be treated at the time of last follow-up. One patient was hematuria, and normal renal function. In contrast, findings treated with CTX followed by MMF and then CSA, one of endocapillary proliferation, segmental sclerosis, crescent Clin J Am Soc Nephrol 9: 1033–1039, June, 2014 IgAN with Minimal Change Disease, Herlitz et al. 1037

formation, and tubulointerstitial scarring are associated with more severe disease that is characterized clinically by more severe proteinuria, in some cases full NS, and renal dysfunction. We report a series of 17 patients with IgAN who pre- sented with NRP or, in most cases, full NS and discor- dant findings of only mild histologic disease. All patients met criteria for IgAN, including mesangial deposits that stained dominantly or codominantly for IgA by immu- fl Renal Function no uorescence, with corresponding mesangial electron dense deposits on ultrastructural evaluation. By light microscopy, 14 biopsies showed mesangial proliferation (82.4%), and glomeruli appeared histologically unre- Stable=7, improved=2, declined=0 Stable=4, improved=1, declined=0 markable in the remaining 3 cases (17.6%). We only in- cluded cases without endocapillary proliferation (E0),

→ necrosis, or cellular crescents. One biopsy exhibited a segmental glomerular scar (which was associated with an old fibrous crescent). The single pathologic finding → ACTH (1) Stable=3, improved=0, declined=0 that correlated with the presentation of full NS was → extensive (median=90%) foot process effacement. The clinical and biopsy findings in these 17 patients, as well MMF – → FK506 (1) as similar cases that have been previously reported (4 17),

→ are most consistent with mild IgAN with superimposed RTX

CTX (1); FK506 MCD. to Steroids → CSA (1); MMF (1); AZA → The combined diagnosis of MCD and IgAN is sup- → Used in Addition ported by the discrepancy between the purely mesangial Alternative Regimens MMF (1) distribution of the immune deposits and the diffuse MMF →

→ nature of the podocyte effacement and severity of pro- CTX steroids (1); CSA teinuria. Mesangial cells may respond to immune de-

CTX (1); CSA CTX MMF (1); CSA posits and release inflammatory that cause mild alterations of the glomerular filtration barrier, but this typically results in only mild, subnephrotic pro-

82 months). Time to remission averaged 4.8 months, with a median time of 2 months. CTX, cyclo- teinuria (26). Hill and colleagues (27,28) have suggested – that aberrantly glycosylated IgA1 can cause mesangial cells to release cytokines that cause podocyte injury, resulting in some of the segmental sclerosis often seen 3 5 3 50%, and still on therapy at the time of last follow-up.

$ in IgAN (although predominantly absent in this series). In the analogous example of lupus (LN), pa- tients with mesangial proliferative LN (class II) who

One or More Relapses present with full NS and extensive foot process efface- Number of Patients with or Treatment Dependence ment in the absence of endocapillary involvement are interpreted as having LN II with superimposed MCD (29) or lupus podocytopathy (30,31). Similarly, we believe that the cases reported herein represent MCD superim- posed on mild underlying IgAN. This interpretation is 9 5 3 further supported by the outcomes in this cohort, where despite the presence of NRP or NS, many patients had a

with Steroids rapid response to steroid therapy, all patients had a Initial Treatment complete or partial response, and no patient developed worsening renal function over a median follow-up of 20 500 mg/d proteinuria and off therapy at the time of last follow-up. 500 mg/d proteinuria and still on therapy at the time of last follow-up. # # months. 3 g/d proteinuria, decrease in proteinuria of 9 5 3

# Several case reports and small series describe findings

Patients similar to those in our series (4–17). Kim et al. (7) iden- tified 12 patients with IgAN who presented with corticosteroid-responsive NS. Eight patients had diffuse podocyte effacement typical of MCD, and the majority a b c of patients had histologically mild IgAN. Response to steroid therapy was prompt (median time=2 months to CR), and a total of seven relapses occurred in five pa- Outcome Category tients. Kim et al. (7) favored the interpretation that their off therapy on therapy on therapy Complete response on therapy: Complete response off therapy: Partial response on therapy: patients had IgAN and MCD rather than an unusual Table 3. Treatment and outcomes Follow-up was available in all 17 patients, witha mean duration of 32b months (range=2.2 c Complete response phosphamide; CSA, cyclosporine; FK506; MMF, mycophenolate mofetil; AZA, azathioprine; RTX, rituximab; ACTH, adrenocorticotrophic hormone. Complete response Partial response variant of IgAN. A series from China reported eight 1038 Clinical Journal of the American Society of Nephrology

cases of mild mesangial proliferative IgAN with NS, and patients treated with CTX, three patients were able to achieve five of six cases with available electron microscopy showed long-term remission off immunosuppressive therapy. extensive podocyte foot process effacement (8). All patients Again, this finding is fully consistent with MCD, where were responsive to corticosteroid therapy, with responses alkylating agents are often the only therapies that can typically occurring within 6–8weeks.Fourpatients elicit a sustained remission or produce longer intervals be- had relapses, and three patients became corticosteroid- tween relapses (39). dependent (8). Qin et al. (16) identified 13 patients with NS in the setting of IgAN is associated with at least two IgAN who had MCD-like changes. Similar to our cohort, distinct patterns of histologic disease. In mild IgAN with their patients had a high level of response to corticosteroids diffuse podocyte foot process effacement, the NS correlates and a high (53.8%) relapse rate, and none of their patients with the degree of effacement, a finding that suggests a progressed to ESRD during a mean follow-up of almost primary podocytopathy and is most consistent with a diag- 5years(16). nosis of mesangial IgAN with superimposed MCD. In A recent Chinese series by Wang et al. (17) enrolled 27 contrast, in cases of more severely proliferative IgAN pre- patients with IgAN and minimal change-like lesions to in- senting with the NS, the prominent endocapillary prolifer- vestigate the use of corticosteroids in this population. All ation and inflammation are likely responsible for the patients achieved a complete response (24-hour urine pro- proteinuria, akin to class III or IV LN with NS. Renal biopsy tein,0.4 g) after 8 weeks of treatment. Unfortunately, only is particularly important to distinguish these two groups, 12 weeks of follow-up data are provided, limiting conclu- because patients with mild IgAN and MCD should receive sions regarding their long-term prognosis (17). treatment directed to MCD and have a more favorable prog- Larger series looking at IgAN with NS encompass a nosis, albeit one that may be associated with a relapsing course heterogeneous population. Han et al. (32) reported 24 pa- and the need for prolonged therapy. We conclude that our tients with NS and IgAN and later included these patients cohort and similar cohorts reported previously (4–17) in a larger series by Kim et al. (33) that comprised 100 pa- comprise a prognostically favorable subset of mild IgAN, in tients with IgAN and NS. Biopsy findings included the full which NS does not predict progressive loss of renal function. spectrum of proliferative lesions, making it a mixed group. We favor the interpretation that such cases represent a dual The primary end point was doubling of SCr, which occurred glomerulopathy, namely mild IgAN and superimposed MCD. in 24% of patients with NS and only 7.1% of patients who did not have NS. Kim et al. (33) concluded that IgAN pa- Acknowledgments tients with NS have a worse prognosis, but it is notable that We thank Drs. S. Zipin, S. Collins, J. Guzzo, L. Jan, S. Kabis, J. Laut, many of the patients had significant proliferative lesions. In A. Bell, S.M. Chen, U. Dalal, R. Tapia, J. Stack, V. Bellot, J. Scherwinter, fact, only four patients had the exclusively mesangial pro- and J. Schwimmer for providing clinical information on their pa- liferative disease and diffuse podocyte foot process efface- tients who were in this cohort. ment that was characteristic of patients in our cohort (33). In the series reported herein, all 17 patients showed a response Disclosures to corticosteroid therapy. Steroids induced an initial CR in 14 None. patients (82%) and a PR in 3 patients (18%). The response to corticosteroids was relatively rapid, with CR occurring in ,2 , References months in 7 patients (41%) and 4 months in 11 patients 1. Tumlin JA, Madaio MP, Hennigar R: Idiopathic IgA nephropathy: (65%). This high frequency and rapidity of responsiveness Pathogenesis, histopathology, and therapeutic options. Clin J Am are similar to the findings reported for adult patients with Soc Nephrol 2: 1054–1061, 2007 MCD. Across several large studies, approximately 75% of 2. D’Amico G: Natural history of idiopathic IgA nephropathy and factors predictive of disease outcome. Semin Nephrol 24: 179– adults with MCD showed a corticosteroid response within – 196, 2004 4months,and75% 93% of patients eventually responded to 3. Barratt J, Feehally J: Treatment of IgA nephropathy. 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Roberts IS, Cook HT, Troyanov S, Alpers CE, Amore A, Barratt J, Maschio G, Cinotti GA, Fuiano G, Schena FP, Castellani A, Della Berthoux F, Bonsib S, Bruijn JA, Cattran DC, Coppo R, D’Agati V, Casa-Alberighi O: Cyclosporin versus cyclophosphamide for D’Amico G, Emancipator S, Emma F, Feehally J, Ferrario F, patients with steroid-dependent and frequently relapsing idio- Fervenza FC, Florquin S, Fogo A, Geddes CC, Groene HJ, Haas pathic nephrotic syndrome: A multicentre randomized con- M, Herzenberg AM, Hill PA, Hogg RJ, Hsu SI, Jennette JC, Joh K, trolled trial. Nephrol Dial Transplant 8: 1326–1332, 1993 Julian BA, Kawamura T, Lai FM, Li LS, Li PK, Liu ZH, Mackinnon B, Mezzano S, Schena FP, Tomino Y, Walker PD, Wang H, Received: November 26, 2013 Accepted: February 20, 2014 Weening JJ, Yoshikawa N, Zhang H; Working Group of the In- ternational IgA Nephropathy Network and the Renal Pathology Published online ahead of print. Publication date available at www. 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