Departments of *Nephrology and Pathology, INSERM Unit 345, and ||INSERM Unit 507, Hôpital Necker, Paris, France, and Department of Pathology, Hôpital Trousseau, Tours, France.
Correspondence to Dr. Bertrand Knebelmann, Department of Nephrology and INSERM Unit U507, Hôpital Necker, 149 Rue de Sèvres, 75743 Paris Cedex 15, France. Phone: 33-14-449-5458; Fax: 33-14-449-5450; E-mail: knebelmann{at}necker.fr
ABSTRACT. Fourteen cases of mesangial IgG glomerulonephritischaracterized by exclusive or predominant mesangial IgG depositsare reported. The median age at onset was 19 yr (range, 13 to47 yr). No patient exhibited evidence of systemic lupus erythematousor other systemic diseases. Proteinuria was present in all cases(median, 2.4 g/d; range, 1 to 13 g/d), microscopic hematuriain 12 cases, and macroscopic hematuria in two cases. Five patientswere hypertensive at the time of referral. In all cases, renalbiopsies revealed mesangial IgG deposits and varying degreesof mesangial matrix expansion, in the absence of significantmesangial cell proliferation. Complement component (mainly C3)deposits were present in virtually all cases. Subepithelialdeposits were also noted in nine cases. IgG deposits were polyclonaland consisted mainly of IgG1 and IgG3 subclasses. In electron-microscopicanalyses, deposits were electron dense and granular. Treatmentwas purely supportive. After a mean follow-up period of 11 yr,seven patients had experienced progression to chronic renalfailure, including four who had reached end-stage renal failure.Three patients exhibited persistently normal renal function.For one patient, a symptomatic recurrence of mesangial IgG depositsin the renal graft was diagnosed 4 yr after renal transplantation.Such a recurrence highlights the specificity of this type ofglomerulonephritis. Mesangial IgG glomerulonephritis is a distinct,albeit rare, type of glomerulonephritis that exhibits far frombenign outcome and may recur in renal transplants.
Glomerular deposits are a major pathologic feature of a widerange of human glomerulonephritides and may be located in themesangial, subepithelial, and subendothelial regions. Variouspatterns of mesangial glomerular deposits have been reported,including those containing Ig, complement components (1), amyloidproteins (2), fibronectin (3), and collagen type III (4). GlomerularIg deposits are encountered in a large number of primary andsecondary glomerulonephritides, such as lupus or cryoglobulinemicnephropathy.
Among primary glomerulonephritides, IgA nephropathy (IgAN),which was first described by Berger and Hinglais (5), is themost common condition associated with mesangial IgA deposits.Another type of primary glomerulonephritis with predominantmesangial Ig deposits has been identified under the eponym IgMnephropathy (6). This condition is characterized by mesangialIgM deposits, but its specificity remains controversial.
Rare cases of primary glomerulonephritis defined by exclusiveor predominant mesangial IgG deposits were reported first bySato et al. (7) and subsequently by Yoshikawa et al. (8). Theclinical and biologic features of this mesangial "IgG nephropathy"remain poorly defined, and its existence as a distinct entityis still questionable. We describe 14 cases of mesangial IgGglomerulonephritis (MIG), with emphasis on long-term renal outcomes,and we report the first recurrence of MIG in a renal transplant.
We reviewed the pathologic findings for all renal biopsies examinedin the Departments of Nephrology and Pathology at HôpitalNecker between 1972 and 2000. Biopsy specimens for light-microscopicanalyses were fixed in Bouin’s solution, embedded in paraffin,and sectioned at 2 µm. The sections were stained withMasson’s trichrome, hematoxylin-eosin, periodic acid-Schiff,and silver methenamine stains. All pathologic features notedin light-microscopic analyses were graded by using a semiquantitativescale (-, absent; ±, very mild; +, mild; ++, moderate;+++, intense).
Tissues for immunofluorescence (IF) analyses were stained withFITC-conjugated, monospecific, anti-human µ, , , , or chain or C3, C1q, or C4 antibodies (Dako, Glostrup, Denmark).The specificity of these antibodies was documented by the absenceof staining of normal kidneys and the blockade of staining byexposure of the tissues to anti-human IgG antibodies. Additionalstaining with monoclonal antibodies against IgG subtypes (agift of Dr. Pierre Aucouturier, INSERM Unit 25, HôpitalNecker, Paris, France) was performed with six biopsy specimens.Direct and indirect IF methods were used, and the intensityof fluorescence was graded (-, absent; ±, very mild;+, mild; ++, moderate; +++, intense). For electron-microscopicanalyses, renal tissues were fixed in glutaraldehyde and osmiumtetroxide, dehydrated, and embedded in Epon 812 resin (GBEMServices, Quebec City, Canada). Ultrathin sections stained withuranyl acetate and lead citrate were examined by using a PhilipsEM300 electron microscope (Philips Medical Systems, Best, TheNetherlands).
Inclusion criteria were based on IF findings. We selected allcases of primary glomerulonephritis with exclusive or predominantmesangial IgG deposits. The diagnosis of primary glomerulonephritiswas made when ongoing infections and systemic diseases, mainlysystemic lupus erythematous (SLE), were excluded. Infectionswere ruled out on the basis of clinical examination resultsand the findings of repeatedly normal erythrocyte sedimentationrates and C-reactive protein levels. American College of Rheumatologyrevised criteria were used for the exclusion of SLE (9). Antinuclearantibodies were detected by indirect IF on Hep2 cells, and anti-DNAantibodies were detected by radioimmunoprecipitation (Farr test).Nephrotic syndrome was defined by heavy proteinuria (>3 g/d),low serum protein concentrations (<60 g/L), and hypoalbuminemia(<30 g/L). Microscopic hematuria was defined by a urinaryerythrocyte count of >10,000 erythrocytes/ml in uncentrifugedurine. The GFR was estimated by using the Cockcroft-Gault formula.Renal failure was defined by a calculated creatinine clearanceof <75 ml/min. High BP was defined as a systolic pressureof 140 mmHg and/or a diastolic pressure of 90 mmHg. All dataare presented as median (range).
Clinical and Laboratory Findings
We reviewed 2693 cases of primary glomerulonephritis diagnosedin our institution between 1972 and 2000. Exclusive or predominantmesangial IgG deposits, in the absence of any evidence of SLE,infections, or other systemic diseases, were noted in 14 cases(Table 1). Six cases of MIG were diagnosed between 1972 and1980, five cases between 1981 and 1990, and three cases between1990 and 2000. There were four female and 10 male patients.The age at onset was 19 yr (range, 13 to 47 yr). The durationof illness at the time of referral was 3 yr (0 to 17 yr). Sixpatients were hypertensive at the time of referral.
Table 1. Clinical characteristics of 14 patients with IgG nephropathy at renal biopsya
At the time of referral, all patients exhibited proteinuria(2.5 g/d; range, 1 to 13 g/d) but only one patient (patient11) manifested signs of nephrotic syndrome. Microscopic hematuriawas observed for 11 patients, whereas bouts of gross hematuriawere observed for two patients (patients 4 and 5). In one case(patient 4), gross hematuria coincided with upper respiratorytract infections. Ten patients exhibited normal renal functionat referral. The serum creatinine concentration was 89 µM(range, 53 to 230 µM), and the creatinine clearance was89 ml/min (range, 40 to 138 ml/min). For all non-nephrotic patients,serum IgG, IgA, and IgM levels were normal. For all patients,CH50, C3, and C4 levels were normal and antinuclear antibodyand/or anti-DNA antibody assays remained negative during thefollow-up period. Repeated serum and urine immunoelectrophoresisdemonstrated no monoclonal Ig component for any of the patients.Assays for cryoglobulinemia yielded negative results for 12tested patients. Hepatitis B virus antigen (HBs) antigen assaysyielded negative results for 12 tested patients and positiveresults for one (patient 8). Anti-hepatitis C virus antibodyassays yielded negative results for eight tested patients.
Pathologic Findings Renal Biopsy at Referral Light Microscopy
Mesangial deposits were detected in all cases (Figure 1) andwere particularly intense in five cases. Varying degrees ofmesangial matrix expansion were present in all cases. Mesangialcell proliferation was not a predominant feature, being mildor absent. Subendothelial deposits were noted for seven patients.Subepithelial deposits of varying abundance were observed fornine patients, including humps in five cases. In all cases,parietal deposits were fewer and smaller than mesangial deposits(Table 2). Silver methenamine staining revealed the presenceof spikes in seven cases and demonstrated a segmental "double-contour"appearance in only one case (patient 12). Segmental glomerularscars were present in six cases. Interstitial fibrosis was observedfor 12 patients, and vascular sclerosis was noted for nine patients.Congo red staining was negative in all cases.
Figure 1. Light-microscopic findings. (A) Patient 4. Initial biopsy; silver methenamine staining. The presence of mesangial deposits (arrows) and mesangial matrix expansion can be observed. The absence of mesangial cell proliferation should be noted. (B) Patient 4. Renal graft biopsy performed 4 yr after renal transplantation. The recurrence of mesangial deposits (arrows) and mesangial matrix expansion can be observed. (C) Patient 14. The presence of mesangial (solid arrow) and subepithelial (dashed arrow) deposits can be observed. Magnifications: x400 in A and C; x1000 in B.
Table 2. Light-microscopic findings in 17 renal biopsies from 14 patients with IgG nephropathya
IF Analyses
Diffuse and granular mesangial IgG deposits (graded + to +++)were present in all cases (Figure 2). Less intense mesangialIgM deposits were noted in five cases, but there were no IgAdeposits (Table 3). Mesangial C3, C4, and C1q were detectedin 14, eight, and 10 cases, respectively. Deposits in the capillarywalls were observed for all patients and consisted of IgG (allcases), IgM (three cases), IgA (two cases), C3 (12 cases), C4(three cases), and C1q (seven cases). Subepithelial deposits(mainly IgG and C3) were present in nine cases. IgG, C3, C4,and C1q deposits along the tubular basement membrane were observedin only one case (patient 1).
Table 3. Characteristics of IF staining in glomeruli from 14 patients (16 biopsies) with IgG nephropathya
Light Chain and IgG Subclass Analyses
IgG subclass and light chain type analyses were performed forsix patients. Positive 1 staining was detected in five cases,2 in one, 3 in five, and 4 in three. IgG1 and -3 were predominant.Both and light chains were present in all cases. No monoclonal or µ deposits were detected (Table 4).
Table 4. Light chain and subclass analysis for six patients with IgG nephropathy
Electron Microscopy
Electron-microscopic findings were available in seven cases.All biopsies revealed the presence of large, electron-dense,granular deposits in the mesangial and perimesangial regions(Figure 3). No organized structure was detected within the deposits.For three patients (patients 3, 6, and 8), similar large subepithelialdeposits were also present. Mesangial cell proliferation wasmild or absent.
Figure 3. Electron-microscopic findings. (a) Patient 4. Large electron-dense deposits in the mesangium can be observed. (Inset) High-magnification view of mesangial deposits, with the peculiar appearance of a granular meshed network. (b) Patient 3. The same peculiar appearance of mesangial deposits as observed for patient 4 should be noted. The presence of rare subepithelial deposits should also be noted. Magnification: x8500 in a; x25,000 in inset.
Repeated Renal Biopsy.
Three patients (patients 1, 12, and 14) underwent two consecutiverenal biopsies (17, 4, and 5 yr apart, respectively). In allthree cases, mesangial deposits and mesangial matrix expansionpersisted in the second renal biopsy. The number of scleroticglomeruli had increased in all cases, whereas tubulointerstitiallesions remained stable. In contrast to the first biopsy, mildmesangial cell proliferation was noted in the second biopsyfor one patient (patient 13) and was associated with segmentaldouble contours in some glomeruli. Subepithelial deposits weremore abundant in the second biopsy for another patient (patient14). The IF study for patient 14 demonstrated that the distributionof IgG subclasses in the mesangial deposits remained identicalto that noted in the first renal biopsy (IgG1 and IgG3).
Patient Outcomes
Six patients (patients 1, 5, 7, 11, 13, and 14) received antihypertensivetherapy. Patients 1, 7, 9, 11, and 14 received an angiotensin-convertingenzyme inhibitor or an angiotensin II AT1 receptor antagonist.No patient received corticosteroids or immunosuppressive drugs.
Four patients (patients 3, 5, 6, and 10) were lost to follow-upmonitoring. For the remaining 10 patients, the mean follow-upperiod was 12 yr (range, 3 to 25 yr) (Table 5). At the lastfollow-up examination, six patients were hypertensive. Fourpatients (patients 2, 4, 12, and 13) reached end-stage renaldisease within 3 to 15 yr after diagnosis, and chronic renalfailure developed in three additional patients (patients 1,7, and 11). Three patients (patients 8, 9, and 14) exhibitedpersistently normal renal function 7 to 25 yr after the recognitionof MIG.
Table 5. Long-term outcomes in mesangial IgG nephropathya
Patients 5 and 13 underwent two consecutive renal transplantations(RT). For patient 5, surgical complications led to rapid lossof the renal graft after the first RT. Four years after thesecond RT, renal graft dysfunction and proteinuria (1.5 g/d)were observed. A renal graft biopsy demonstrated the recurrenceof mesangial deposits and mesangial matrix expansion in theabsence of mesangial cell proliferation (Figure 1). Mild interstitialand vascular sclerosis was present. No glomerular or interstitialcellular infiltrate was noted. In IF studies, mesangial andparietal IgG (scored ++), C3 (scored ++), C4, and C1q depositswere detected. No mesangial IgA or IgM deposits were noted.
Patient 13 lost her first renal graft because of severe acuterejection 1.5 yr after RT. Her second RT has been uneventfulto date, and no renal graft biopsy has been performed.
MIG as a Distinct Pathologic Entity
Glomerular mesangial IgG deposition occurs in various typesof primary and secondary glomerulonephritides, including lupusnephritis (10) and mesangiocapillary nephropathy (11). In IgAN,the most common type of primary glomerulonephritis, IgG (mainlyIgG1 and IgG3) is codeposited with IgA in up to 40% of cases(12).
The first adult cases of primary glomerulonephritis characterizedby exclusive or predominant mesangial IgG deposits were observedin Japan by Sato et al. (7). Subsequently, Yoshikawa et al.(8) reported 10 pediatric cases of MIG. The report by Sato etal. (7) included only six adult patients, with a relativelybenign course of MIG after a median follow-up period of 4.9yr (Table 6). This small number of reported adult cases, therelatively limited follow-up periods, and probably the indolentcourse of nephropathy were the limiting factors for the characterizationof MIG as a distinct primary glomerulonephritis. Here we reportthe largest series of MIG cases to date, including 14 cases.Ten of our patients underwent extended follow-up monitoring,with a mean follow-up period of 11.5 yr; four patients weremonitored for >15 yr. In our series, the course of MIG wasfar from benign, inasmuch as chronic renal failure occurredin one-half of the patients. In addition, we describe the firstrecurrence of mesangial IgG deposits in a renal graft. Suchrecurrence supports the notion that MIG is a distinct type ofprimary glomerulonephritis.
Table 6. Clinical features and renal outcomes in reported series of MIGa
The prevalence of MIG among primary glomerulonephritides diagnosedat our institution between 1972 and 2000 was approximately 0.5%.Our data are in accordance with the previous reports of incidencesof 0.54% in adults (7) and 1.1% in children (8) and contrastwith the high frequency of IgAN (13). However, the incidenceof MIG may be underestimated, because patients with mild urinaryabnormalities do not undergo renal biopsies. In our series,nine patients exhibited normal renal function at the time ofreferral, and renal biopsies were performed because of significantproteinuria and microscopic and/or macroscopic hematuria. Medianproteinuria at referral was 2.5 g/d, with the nephrotic syndromebeing noted for one patient. Our data are in contrast to themild proteinuria (0.7 g/L) noted in the six cases of IgG nephropathyreported by Sato et al. (7). Interestingly, in one case (patient4), recurrent episodes of gross hematuria occurred during upperrespiratory tract infections, producing a striking clinicalresemblance to IgAN.
All 14 cases of MIG presented here share two prominent pathologicfeatures, i.e., the presence of exclusive or predominant mesangialIgG deposits and mesangial matrix expansion. IgG deposits exhibiteda uniform appearance in light- and electron-microscopic studies.In a large control necropsy study by Sinniah (14), isolatedmesangial IgG deposits were not detected, in contrast to IgAand IgM. Moreover, for three of our patients (patients 1, 12,and 14), repeated renal biopsies (performed 17, 4, and 5 yr,respectively, after the first biopsy) revealed persistent mesangialIgG deposits, with the presence of the same IgG subclasses inthe only tested case (patient 14). Therefore, we think thatIgG deposits were not coincidental in our cases and are pathogenicallyrelevant.
Mesangial deposition of complement components, mainly C3 andC1q, was present in almost all cases. Similar patterns of complementcomponent deposition in the mesangium were observed by Satoet al. (7) and Yoshikawa et al. (8). C3 mesangial depositionis a common pathologic feature of other Ig deposit-related,primary glomerulonephritides and occurs in almost all casesof IgAN (14). However, in contrast to MIG, C4 and C1q depositsare uncommon in IgAN.
In our series, as well as in previously reported cases (7,8),the extensive Ig and complement deposition contrasts with theabsence of marked mesangial cell proliferation. This absenceof endo- and extracapillary cell proliferation is in strikingcontrast to IgAN, in which mesangial cell proliferation andcrescents are observed in 36 and 26% of cases, respectively(15,16).
Segmental parietal deposits (subendothelial and subepithelial)were detected in more than one-half of our patients. Parietaldeposits were mild in all cases except in the second renal biopsyfor patient 14. In contrast, in the report by Sato et al. (7),IgG deposits were exclusively located in the mesangium. In theirpediatric series, Yoshikawa et al. (8) did not observe parietaldeposits in IF analyses but observed subepithelial, subendothelial,and intramembranous deposits for nine of 10 patients in electron-microscopicstudies.
Differential Diagnosis
The recognition of this disease as a new type of glomerulonephritisrequires the careful exclusion of other types of glomerulonephritides.There was no marked mesangial cell proliferation in any case,and mesangial interposition was present in a single case (patient12) in a repeat renal biopsy performed during advanced renalfailure. These pathologic features exclude the diagnosis ofmesangiocapillary glomerulonephritis, another type of primaryglomerulonephritis associated with glomerular deposition ofIg and complement. We also excluded the diagnosis of membranousnephropathy, although subepithelial deposits and spikes wereobserved for nine of our patients. Indeed, the subepithelialdeposits noted in some of our cases were focal, fewer in number,and smaller in size, compared with mesangial deposits. Similarly,such mild subepithelial deposits are common in IgAN, occurringin 18 to 56% of cases (17,18). Moreover, several studies haveestablished the IgG4 subclass as the most constantly presentIgG subclass in glomerular deposits (19,20). This contrastswith our MIG cases, in which IgG4 deposits were observed inonly one tested case. The humps noted in six of our cases maysuggest the diagnosis of postinfectious glomerulonephritis.However, humps are not pathognomonic of postinfectious glomerulonephritisand are encountered in various nephropathies, including somecases of IgAN (17). No clinical or biologic features of ongoinginfection were noted for any patient during extended follow-upmonitoring. Marked mesangial proliferation and low complementlevels, two main features of postinfectious glomerulonephritis,were absent in all of our cases. Finally, the recurrence ofMIG in patient 5 argues against the diagnosis of postinfectiousglomerulonephritis. Therefore, we rejected the possibility ofpostinfectious glomerulonephritis. Mesangial C1q deposits, whichwere detected in all of our cases, could suggest C1q nephropathy,as first described by Jennette et al. (21). However, C1q nephropathyis characterized by the glomerular deposition of C1q, as a predominantcomplement component, and various types of Ig. The oppositeis true in our MIG cases and in those reported by Sato et al.(7) and Yoshikawa et al. (8), in which mesangial deposits consistof IgG, as a predominant or exclusive Ig, and various complementcomponents (C3, C1q, and C4). Therefore, MIG is clearly differentfrom C1q nephropathy. Mesangial IgG glomerular deposits arealso encountered in lupus nephritis and fibrillary/immunotactoidglomerulopathy. Lupus nephritis is characterized by the extensiveglomerular deposition of Ig and complement, leading to mesangialcell proliferation. Despite the prolonged duration of illnessat the time of referral and/or follow-up examinations, clinicaland serologic features of SLE (or any other systemic disease)were repeatedly absent among our patients. Moreover, the absenceof any mesangial proliferation in MIG cases, contrasting withthe severe renal abnormalities of some patients, argues againstthe diagnosis of lupus nephritis. Therefore, the diagnosis of(latent) lupus nephropathy can be reasonably excluded for ourpatients.
Glomerular IgG deposits may occur as organized fibrillar (fibrillaryglomerulonephritis) (22) or microtubular (immunotactoid glomerulonephritis)(23) deposits. The cases reported herein are clearly differentfrom fibrillar/immunotactoid cases, for the following reasons.(1) Electron-microscopic studies for seven of seven of our patientsrevealed large electron-dense deposits in the absence of microtubularor fibrillary aggregates. (2) Whereas immunotactoid glomerulonephritisis characterized by monoclonal IgG deposits, mesangial IgG depositswere polyclonal in IF analyses for six of six of our patients(Table 4). (3) In contrast to fibrillary glomerulonephritis,in which IgG deposits are exclusively of the 4 subclass (24),1 and 3 were the predominant subclasses within the mesangiumfor all of our tested patients. (4) For all of our patients,long-term follow-up monitoring failed to reveal monoclonal gammopathyor lymphoproliferative disorder, which are frequently associatedwith immunotactoid glomerulopathy.
The pathogenesis of MIG remains unclear. Mesangial IgG depositiondoes not seem to be related to increased serum IgG levels, becauseall non-nephrotic patients exhibited normal IgG levels. It maybe speculated, as for IgA1 in IgAN (13), that specific biochemicalabnormalities of IgG1 and -3 may lead to their deposition inthe mesangium. This glomerular IgG deposition may lead to eitherimmunotactoid glomerulonephritis or MIG, depending on the predominantIgG subtype(s).
MIG Prognosis
For our patients, treatment was purely supportive and consistedof an antihypertensive and/or antiproteinuric regimen, includingangiotensin-converting enzyme inhibitors or angiotensin II receptorantagonists for five patients. In the report by Sato et al.(7), all patients presented with normal renal function and mildproteinuria and therefore did not receive immunosuppressivetreatment. In a case report (25), the nephrotic syndrome inan adult patient with MIG was resistant to corticosteroid andcyclophosphamide treatment. In the report by Yoshikawa et al.(8), four children with MIG, nephrotic syndrome, and normalrenal function were treated with a corticosteroid regimen, withcomplete or partial remission in two cases. It remains to beestablished whether steroid treatment could prevent or slowthe progression of severe MIG, as recently reported for IgAN(26).
At the last follow-up examination, one-half of the patientshad progressed to chronic renal failure and four had reachedend-stage renal disease. These data are in sharp contrast toprevious reports that suggested a relatively benign course forMIG (7,8). In our series, renal function remained normal intwo patients, despite persistent urinary sedimentation abnormalities.Therefore, as for IgAN, the prognosis of MIG is highly variableamong patients.
One of the most striking features of this series is the recurrenceof MIG after RT in one patient (patient 4) (Figure 1). In light-microscopicand IF studies, mesangial deposits in the renal graft were verysimilar to those noted in the native kidney. This is the firstreport of MIG recurrence in a renal transplant recipient. Asfor IgAN, recurrence after RT was probably the last missingelement of proof for the identification of MIG as a distincttype of glomerulonephritis.
In summary, MIG is a very rare but distinct type of primaryglomerulonephritis that is characterized by exclusive or predominantmesangial IgG deposits. Its renal prognosis may be less favorablethan previously reported. Nephrologists should be aware of thepossibility of recurrence in renal grafts.
Acknowledgments
We thank Drs. Yvon Lebranchu and Bruno Perronne for collaborationand Doreen Broneer, Victoria Hauzy Nagel, and Martine Netterfor invaluable secretarial help.
Imbasciati E, Gherardi G, Morozumi K, Gudat F, Epper R, Basler V: Collagen type III glomerulopathy: A new idiopathic glomerular disease. Am J Nephrol 11: 422–429, 1991[Medline]
Saha H, Mustonen J, Pasternack A, Helin H: Clinical follow-up of 54 patients with IgM-nephropathy. Am J Nephrol 9: 124–128, 1989[Medline]
Sato M, Kojima H, Nabeshima K, Nakajima Y, Koshikawa S: Primary glomerulonephritis with predominant mesangial immunoglobulin G deposits: A distinct entity? Nephron 64: 122–128, 1993[Medline]
Yoshikawa N, Iijima K, Shimomura M, Nakamura H, Ito H: IgG-associated primary glomerulonephritis in children. Clin Nephrol 42: 281–287, 1994[Medline]
Hochberg MC: Updating the American College of Rheumatology revisited criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40: 1725, 1997[Medline]
Cameron JS: Lupus nephritis. J Am Soc Nephrol 10: 413–424, 1999[Free Full Text]
Chan MK, Chan KW, Chan PC, Fang GX, Cheng IK: Adult-onset mesangiocapillary glomerulonephritis: A disease with a poor prognosis. Q J Med 72: 599–607, 1989[Abstract/Free Full Text]
Aucouturier P, Monteiro RC, Noel LH, Preud’homme JL, Lesavre P: Glomerular and serum immunoglobulin G subclasses in IgA nephropathy. Clin Immunol Immunopathol 51: 338–347, 1989[CrossRef][Medline]
Floege J, Feehally J: IgA nephropathy: Recent developments. J Am Soc Nephrol 11: 2395–2403, 2000[Free Full Text]
Sinniah R: Occurrence of mesangial IgA and IgM deposits in a control necropsy population. J Clin Pathol 36: 276–279, 1983[Abstract/Free Full Text]
Terasaki T, Sano M, Narita M, Tojo S: Ultrastructural study of gaps of the glomerular basement membrane in IgA nephropathy. Am J Nephrol 6: 443–449, 1986[Medline]
Alamartine E, Sabatier JC, Berthoux FC: Comparison of pathological lesions on repeated renal biopsies in 73 patients with primary IgA glomerulonephritis: Value of quantitative scoring and approach to final prognosis. Clin Nephrol 34: 45–51, 1990[Medline]
Lee HS, Choi Y, Lee JS, Yu BH, Koh HI: Ultrastructural changes in IgA nephropathy in relation to histologic and clinical data. Kidney Int 35: 880–886, 1989[Medline]
Clarkson AR, Seymour AE, Thompson AJ, Haynes WD, Chan YL, Jackson B: IgA nephropathy: A syndrome of uniform morphology, diverse clinical features and uncertain prognosis. Clin Nephrol 8: 459–471, 1977[Medline]
Noël LH, Aucouturier P, Monteiro R, Preud’homme JL, Lesavre P: Glomerular and serum immunoglobulin G subclasses in membranous nephropathy and anti-glomerular basement membrane nephritis. Clin Immunol Immunopathol 46: 186–194, 1988[CrossRef][Medline]
Doi T, Mayumi M, Kanatsu K, Suehiro F, Hamashima Y: Distribution of IgG subclasses in membranous nephropathy. Clin Exp Immunol 58: 57–62, 1984[Medline]
Jennette JC, Hipp CG: C1q nephropathy: A distinct pathologic entity usually causing nephrotic syndrome. Am J Kidney Dis 6: 103–110, 1985[Medline]
Korbet SM, Schwartz MM, Lewis EJ: The fibrillary glomerulopathies. Am J Kidney Dis 23: 751–765, 1994[Medline]
Korbet SM, Schwartz MM, Lewis EJ: Immunotactoid glomerulopathy. Am J Kidney Dis 17: 247–257, 1991[Medline]
Iskandar S, Falk R, Jennette C: Clinical and pathological features of fibrillary glomerulonephritis. Kidney Int 42: 1401–1407, 1992[Medline]
Pozzi C, Bolasco PG, Fogazzi GB, Andrulli S, Altieri P, Ponticelli C, Locatelli F: Corticosteroids in IgA nephropathy: A randomised controlled trial. Lancet 353: 883–887, 1999[CrossRef][Medline]
Received for publication April 11, 2001.
Accepted for publication September 12, 2001.
This article has been cited by other articles:
A. Servais, V. Moriniere, J.-P. Grunfeld, L.-H. Noel, J.-M. Goujon, B. Chadefaux-Vekemans, and C. Antignac Late-Onset Nephropathic Cystinosis: Clinical Presentation, Outcome, and Genotyping
Clin. J. Am. Soc. Nephrol.,
January 1, 2008;
3(1):
27 - 35.
[Abstract][Full Text][PDF]
Top
Abstract
Introduction
, 
, 
, or 
chain or C3, C1q, or C4 antibodies (Dako, Glostrup, Denmark). The specificity of these antibodies was documented by the absence of staining of normal kidneys and the blockade of staining by exposure of the tissues to anti-human IgG antibodies. Additional staining with monoclonal antibodies against IgG subtypes (a gift of Dr. Pierre Aucouturier, INSERM Unit 25, Hôpital Necker, Paris, France) was performed with six biopsy specimens. Direct and indirect IF methods were used, and the intensity of fluorescence was graded (-, absent; ±, very mild; +, mild; ++, moderate; +++, intense). For electron-microscopic analyses, renal tissues were fixed in glutaraldehyde and osmium tetroxide, dehydrated, and embedded in Epon 812 resin (GBEM Services, Quebec City, Canada). Ultrathin sections stained with uranyl acetate and lead citrate were examined by using a Philips EM300 electron microscope (Philips Medical Systems, Best, The Netherlands). 
140 mmHg and/or a diastolic pressure of 
0.7 g/L) noted in the six cases of IgG nephropathy reported by Sato et al. (7). Interestingly, in one case (patient 4), recurrent episodes of gross hematuria occurred during upper respiratory tract infections, producing a striking clinical resemblance to IgAN. 
