Focal Segmental Glomerulosclerosis in Nephrotic Adults: Presentation, Prognosis, and Response to Therapy of the Histologic Variants
Micky J. Chun*,
Stephen M. Korbet*,
Melvin M. Schwartz and
Edmund J. Lewis*
Departments of *Medicine, and Pathology, Rush University Medical Center, Chicago, Illinois
Correspondence to Dr. Stephen M. Korbet, 1426 W. Washington Boulevard, Chicago, IL 60607. Phone: 312–850–8434; Fax: 312–850–8434; E-mail: Skorbet{at}aol.com
ABSTRACT. The histopathologic diagnosis of primary focal segmentalglomerulosclerosis (FSGS) has come to include a number of histologiclesions (variants), but the prognostic significance of thesediscrete lesions is controversial because published informationregarding the presentation, course, and response to treatmentis limited. A retrospective analysis was conducted of 87 nephroticadult patients with biopsy-proven primary FSGS. Patients werecategorized on the basis of histologic criteria into those witha classic scar (36 patients), the cellular or collapsing lesion(40 patients), or the tip lesion (11 patients) of FSGS to evaluatedifferences in presentation, response to therapy, and clinicaloutcomes. The clinical features at biopsy were similar amongthe three groups with the exception that patients with the tiplesion were older and patients with the collapsing lesion hadmore severe proteinuria. Over the course of follow-up, 63% ofpatients treated attained remission and the response to steroidtherapy was similar among the groups (classic scar 53% versuscollapsing lesion 64% versus tip lesion 78%; P = 0.45). Theoverall renal survival was significantly better for patientswho entered remission compared with patients who did not enterremission (92% versus 33% at 10 yr; P < 0.0001). The renalsurvival at 10 yr for patients who entered remission was similaramong the three groups (classic scar 100% versus tip lesion100% versus collapsing lesion 80%; P = 0.61). In patients whodid not enter remission, the renal survival at 10 yr was significantlyworse for patients with collapsing lesion and tip lesion (classicscar 49% versus tip lesion 25% versus collapsing lesion 21%;P = 0.002). In conclusion, the prognosis for nephrotic FSGSpatients who enter remission is excellent regardless of thehistologic lesion. Because the remission rate after treatmentis similar among patients with the histologic variants, responseto therapy cannot be predicted on the basis of histology alone.Thus, nephrotic patients with primary FSGS should receive atrial of therapy irrespective of the histologic lesion whennot contraindicated.
Focal segmental glomerulosclerosis (FSGS) is a pattern of injurydefined by a segmental scar, which involves some but not allglomeruli. When all of the secondary causes of this patternof injury are eliminated, the remaining patients receive a diagnosisof primary FSGS. Although patients with primary FSGS may presentwith any level of proteinuria, clinical concern is greatestfor those who present with nephrotic-range proteinuria becausewithout treatment, they have an extremely poor prognosis, progressingto ESRD over the course of 3 to 6 yr (1,2). However, it is widelyrecognized that the prognosis in nephrotic patients with primaryFSGS is significantly improved when remission of proteinuriais achieved. Because >50% of nephrotic adult patients withFSGS respond to an aggressive course of steroids, a trial oftherapy has been recommended (1,3–5).
Over the last 20 yr, in addition to the "classic" segmentalscar, a number of histologic lesions or variants have been includedin the diagnosis of primary FSGS, most notably the cellularor collapsing lesion and the tip lesion (6–10). The importanceof recognizing these variants is the putative difference inprognosis and therapeutic response associated with the differentlesions. Recently, a pathologic classification of FSGS has beenproposed (7,9), but the prognostic and therapeutic utility ofsuch a classification remains controversial (11,12), largelybecause studies that have assessed the clinical relevance ofthe histologic variants of primary FSGS in nephrotic patientsare few and conflicting (6,13–17).
We previously published our experience with the cellular lesionin adults with primary FSGS, which found that the response totherapy and outcome for patients in remission were similar topatients with the classic scars of FSGS (16). We now presentour enlarging experience in nephrotic adults with primary FSGS,with increased follow-up, to evaluate the importance of thetip and cellular or collapsing lesions of FSGS.
We conducted a retrospective, clinicopathologic analysis ofadult patients (>15 yr of age at presentation) who had primaryFSGS and nephrotic-range proteinuria (>3 g/d) and were seenby the Renal Pathology Service and followed by the Section ofNephrology at Rush University Medical Center (Chicago, IL) between1975 and 2001. The diagnosis of primary FSGS was establishedwhen there was no immunopathologic or ultrastructural evidencefor another primary glomerular disease or a systemic diseaseassociated with secondary segmental glomerular sclerosis andwhen review of the medical records of each patient revealedno evidence of systemic disease, other diseases associated withglomerulopathy, morbid obesity, reflux, HIV infection, nephrectomy,solitary kidney, intravenous drug abuse, or a family historyof renal disease. On the basis of these criteria, we identifieda total of 117 patients with primary FSGS; nephrotic-range proteinuriawas present in 87 of these patients, and they form the basisof this study.
Definition of FSGS and Pathology Studies
Inclusion in this study required a minimum of five glomeruliin the light microscopic section. The pathologic diagnosis ofFSGS was established by the finding of at least one glomeruluswith a segmental lesion, and some of the remaining glomeruliwere relatively normal. Although the segmental nature of thislesion was usually obvious, we accepted a lesion as segmentalwhen at least one unscarred lobule with patent capillaries waspresent in the involved glomerulus. Three morphologic formsof FSGS were included: the classic scar (Figure 1), the cellularor collapsing lesion (Figure 2), and the tip lesion (Figure 3).
Figure 1. Classic focal segmental glomerulosclerosis (FSGS). A segmental scar with an adhesion to Bowman’s capsule and hyalinosis is present in the perihilar region of the glomerulus. Hilar arteriole (*). Magnification, x66, periodic acid-Schiff (PAS) stain.
Figure 2. The cellular lesion of FSGS. The entire glomerular tuft shows collapse of capillaries and proliferation, hypertrophy, and vacuolization of the visceral epithelium. Afferent arteriole at the juxtaglomerular apparatus (*). Magnification, x66, PAS stain.
Figure 3. The tip lesion of FSGS. A single glomerular lobule is adherent to Bowman’s capsule at the origin of the proximal tubule (). The involved capillaries are occluded by foamy macrophages, and the uninvolved glomerulus has patent capillaries and normal mesangial matrix and cellularity. Hilar arterioles (*). Magnification, x66, PAS stain.
The classic scar is defined by a segmental scar that is locatedeither at the hilum or in the glomerular periphery. The scarcomprises either the obliteration of the glomerular architectureand replacement by collagen or segmental glomerular collapsewithout a "cellular" lesion. The overlying parietal and visceralepithelium may be prominent, especially when associated withan adhesion, but it is not stratified. This lesion is frequentlyassociated with hyalinosis and adhesions. The finding of a cellularor a tip lesion (see below) excludes the biopsy from the classicscar category.
We use the term "cellular" lesion as we originally defined itin 1985 (18), and it is identical to collapsing lesion (12,19)described by Weiss et al. (20), Detwiler et al. (13), and Valeriet al. (17). The diagnosis of "cellular" FSGS requires at leastone glomerulus with segmental or global glomerular collapsewith hypertrophy and hyperplasia of the overlying visceral epithelium.Collapse means that the glomerular capillaries are obliteratedwith loss of endothelium, wrinkling, and folding of the glomerularbasement membranes without destruction or replacement with excesscollagen. The hypertrophic epithelial cells have vesicular nucleiwith prominent nucleoli and copious, basophilic cytoplasm withvacuoles, and periodic acid-Schiff (PAS)–positive droplets.Epithelial hyperplasia is evidenced by stratification of oftenpoorly cohesive cells that have occasional mitoses. Involvedglomeruli may show segmental endocapillary hypercellularitywith foam cells and macrophages, and adhesions are occasionallypresent. In contrast, D’Agati et al. (7–9) definedthe cellular lesion as a glomerulus with a segmental endocapillaryhypercellularity in the absence of hypertrophy and hyperplasiaof the overlying epithelial cells. We (S.M.K. and M.M.S.) reviewedthe slides of every patient in this series and found none thatwould be classified as a cellular lesion by the recently proposedclassification (7,9). Thus, for the remainder of this article,the cellular and collapsing lesions are considered to be synonymous.Classic scars and global sclerosis are frequently seen alongwith the cellular/collapsing lesion of FSGS.
The "tip lesion" variant of FSGS is defined by segmental glomerularpathology that involves the tubular pole of Bowman’s capsule(the origin of the proximal tubule must be present in at leastone involved glomerulus). As originally described by Howie etal. (21), the lesion is small, involving only one glomerularlobule or a few capillaries, and there is an adhesion betweenthe involved, distal tuft and the parietal epithelium or theunderlying stroma at the tubular pole of the glomerulus. Thesegmental glomerular pathology includes capillary collapse,infiltration with foam cells and macrophages, and proliferationand hypertrophy of the overlying podocytes. As defined, thereis overlap of the pathologic features seen in the tip and thecellular lesions, but the tip lesion is distinguished by itssmall size and location. Global sclerosis and classic lesionsmay occur in cases of the tip lesion, but a cellular lesionexcludes the biopsy from this category.
Renal biopsy tissue was divided and processed for light, fluorescence,and electron microscopy. Fluorescence and electron microscopywas used to exclude nonprimary causes of FSGS, but the lightmicroscopic examination of slides stained with hematoxylin andeosin, Masson’s trichrome, PAS, and methenamine silver–PAS(Jones stain) provided the diagnosis of FSGS and categorizationinto one of the three groups. The percentage of interstitialfibrosis was calculated using an ocular grid and point-countingon trichrome stained sections of renal cortex. The renal pathologist(M.M.S.), who was blinded to the clinical data, performed thehistologic evaluation. The pathologic classification of the87 nephrotic adults was as follows: classic scars, 36 patients(41%); cellular lesion, 40 patients (46%); and tip lesion, 11patients (13%).
Clinical Studies and Laboratory Examination
Demographic, clinical, and laboratory information at the timeof renal biopsy and at follow-up was obtained on each patient.Clinical records were reviewed to determine the patients’race, gender, age, BP, level of protein excretion, serum creatinine,and serum albumin at the time of biopsy. Presentation was definedas the time when proteinuria was first detected. Renal insufficiencywas defined as a serum creatinine >1.3 mg/dl. ESRD was definedas a serum creatinine 5 mg/dl or the need for renal replacementtherapy. The level of proteinuria at the time of biopsy wascategorized as (1) nephrotic-range proteinuria defined as >3g/d protein and (2) massive proteinuria defined as >10 g/dprotein. Nephrotic syndrome was defined as nephrotic-range proteinuriaand hypoalbuminemia (3.5 g/dl). Hypertension was defined asa systolic BP >140 mmHg and a diastolic BP >90 mmHg. Inpatients with nephrotic proteinuria, complete remission wasdefined as a urine protein of 0.3 g/d, and partial remissionwas defined as a urine protein between 0.31 and 2.5 g/d.
Treatment
The decision to treat patients with immunosuppressive therapy,including corticosteroids, was based solely on physician discretion.A total of 51 (59%) patients received treatment. From 1975 to1994 50% (31 of 62) of patients received treatment. In 1994,we reviewed the response to therapy in primary FSGS (22) andthereafter recommended a trial of steroid therapy in nephroticpatients with primary FSGS in whom renal function is well preserved(serum creatinine <3 mg/dl) and in whom it is not contraindicated(e.g., morbid obesity, diabetes). From 1994 to 2001, 80% (20of 25) of patients seen received treatment. Although no specifictherapeutic regimen was used, we proposed a more aggressiveapproach to the treatment of nephrotic adults with primary FSGS.This comprises an initial course of prednisone given at a doseof 1 mg/kg per day (up to 80 mg) for 3 to 4 mo. In patientswho demonstrated complete or partial remission, the dose ofprednisone was then tapered slowly over 2 to 3 mo. Patientswho were unresponsive to the initial therapy were tapered offprednisone more rapidly, over 4 to 6 wks. To minimize toxicityin the elderly, an alternate-day prednisone regimen (1 to 2mg/kg up to 120 mg) was used for 4 to 5 mo.
Statistical Analyses
Categorical data were analyzed using the 2 test. Mann-Whitneyand ANOVA using Dunn multiple comparison tests were used forevaluating the continuous data. Renal survival time from thedate of biopsy to ESRD was determined by product-limit life-tabledistributions and compared using a log-rank test. Data are reportedas a mean ± SD. P < 0.05 is considered significant.
Clinical Characteristics
The clinical characteristics at biopsy of the 87 nephrotic patients,based on their histologic classification (classic scars, 36[41%] patients; cellular lesion, 40 [46%] patients; and tiplesion, 11 [13%] patients), are shown in Table 1. The demographicfeatures (race and gender) were similar among the three groupswith the exception that patients with the tip lesion were olderat biopsy. The level of proteinuria, the proportion of patientswith proteinuria >10 g/d, and the degree of hypoalbuminemiawere significantly greater in patients with the cellular lesioncompared with those patients with the classic scar. Patientswith the tip lesion had more hypoalbuminemia than patients withthe classic scar, but the severity of proteinuria was not significantlydifferent. The time from presentation to biopsy was shortestin patients with the tip lesion, but this was not significantlydifferent from patients with classic scars or cellular lesions.
Pathology Studies
The pathologic features are shown in Table 2. The overall averagenumber of glomeruli for evaluation by light microscopy was 25± 17 (in 90% of biopsies, there were 10 glomeruli), andthis was similar among the three groups of patients. The proportionof glomeruli with classic segmental scars was significantlylarger in patients with classic FSGS compared with patientswith cellular (19 patients had classic segmental scars) or tiplesions (one patient had classic segmental scars). In patientswith classic FSGS, classic segmental scars involved <20%(12 ± 5%; median, 12%) of glomeruli in 27 (75%) patientsand 20% (27 ± 4%; median, 26%) of glomeruli in nine (25%)patients. In patients with the cellular lesion, the overallproportion of glomeruli with segmental or global cellular lesionswas 22 ± 18%. In the majority of patients (24 patients[60%]) with the cellular lesion, the proportion of glomeruliwith cellular lesions (segmental plus global) was <20% (10.6± 4%; median, 11%) of glomeruli. Segmental and globalcellular lesions involving 20% (39 ± 17%; median, 33%)of glomeruli was observed in 16 (40%) patients. The percentageof cortical interstitial fibrosis was similar among the threegroups. There was no significant difference in the percentageof interstitial fibrosis among patients with classic or cellularlesion on the basis of the degree of involvement (<20% versus20% classic or cellular lesions).
Clinical Course and Outcome
A total of 51 (59%) patients were treated with steroids (Table 3).On average, patients received high-dose prednisone therapy(60 mg/d) for 3.18 ± 1.49 mo (mean ± SD; median,3.00), and the total course of therapy, including the steroidtaper was 8.99 ± 9.93 mo (mean ± SD; median, 6.00mo). Although the proportion of patients who were treated wasnot significantly different among the groups (P = 0.1), a largerproportion of patients with the tip lesion were treated comparedwith patients with classic FSGS or the cellular lesion. Theduration of high-dose prednisone therapy was not significantlydifferent among the three groups: classic scar, 3.26 ±2.04 mo (median, 3.00); cellular lesion, 3.35 ± 1.16mo (median, 3.00); and tip lesion, 2.57 ± 1.00 mo (median3.00). The total therapeutic course also was not significantlydifferent among the three groups: the classic scar, 12.03 ±14.54 mo (median, 9.00); the cellular lesion, 6.83 ±3.21 mo (median, 6.5); tip lesion, 9.00 ± 10.85 mo (median5.00). In addition to steroids, 11 patients received cyclophosphamideor cyclosporin as part of the initial course of therapy. Theproportion of patients who received these agents was not significantlydifferent among the three groups (four patients with classicFSGS, six with the cellular lesion, and one with the tip lesion;P = 0.7).
Clinical and pathologic features of the treated patients areshown in Tables 4 and 5. There were no significant differencesamong the groups in the clinical features at biopsy in treatedpatients (Table 4). The degree of interstitial fibrosis andglobal sclerosis was similar among the groups, but the proportionof glomeruli with classic segmental scars was highest in patientswith classic FSGS, and patients with cellular FSGS had a greaterproportion of glomeruli with any glomerular lesion comparedwith patients with tip lesions (Table 5).
The duration of follow-up was similar among the three groups(Table 3). Remission (complete or partial) was attained in 32(63%) patients treated (Table 3). The overall response to treatmentamong the three groups was not different; however, a largerproportion of patients with the tip lesion attained completeremission (five patients [55%]) compared with patients withclassic FSGS (six patients [35%]) or the cellular lesion (sixpatients [24%]). The remission rate in patients who had classicFSGS with segmental scars involving 20% of glomeruli was 50%(two of four treated patients) compared with 54% (seven of 13treated patients) for patients with <20% involvement withclassic segmental scars (NS). The remission rate in patientswith the cellular lesion involving 20% of glomeruli was 33%(four of 12 treated patients) compared with 92% (12/13 treatedpatients) for patients with <20% involvement with cellularlesions (P = 0.008). Of the 36 patients who were not treated,remission (spontaneous) was observed in only four (11%) patients,and in all cases, these were partial remissions (63% remissionrate for treated versus 11% for untreated patients; P = 0.0001).
Progression to ESRD was observed in a total of 29 (33%) patients,and the proportion of patients who progressed to ESRD was greatestin patients with the cellular lesion. Overall, progression toESRD was significantly greater in patients who did not attainremission compared with patients who attained remission (53%[27 of 51] versus 6% [2 of 36]; P < 0.0001), and this wasa consistent finding irrespective of the lesion (Table 3). Theproportion who progressed to ESRD for patients in remissioncompared with those who were not in remission was 9 versus 32%(P = 0.2) for patients with the classic lesion, 6 versus 73%(P < 0.0001) for patients with cellular lesions, and 0 versus75% (P < 0.05) for patients with tip lesions. Progressionto ESRD was significantly higher in the 36 patients who didnot receive treatment (17 of 36 patients [47%]) compared withthose who received a course of therapy (12 of 51 patients [24%];P < 0.05; Table 3).
The overall renal survival at 5 and 10 yr in patients who attainedremission was 100% and 92%, respectively (Figure 4). In patientswho attained remission, the renal survival at 5 and 10 yr was100% in patients with classic FSGS and the tip lesion and 100%and 80%, respectively, for patients with the cellular lesion(Figure 5). In patients who did not attain remission, the overallrenal survival at 5 and 10 yr was significantly poorer, at 45%and 33%, respectively (P < 0.0001; Figure 4). The renal survivalat 5 and 10 yr in patients who did not attain remission was76% and 49% in patients with classic FSGS, 21% each for patientswith cellular lesions, and 25% (5 yr) for patients with tiplesions (P = 0.002; Figure 6). The poorer renal survivals observedfor nonremitting patients with cellular and tip lesions persistedeven when adjusted for the level of proteinuria at baseline.Of the four patients who had tip lesion and did not enter remission,three progressed to ESRD at 11, 18, and 30 mo. The remainingpatient had good renal function at last follow-up at 59 mo.
Figure 4. Renal survival in nephrotic FSGS patients based on remission status (P < 0.0001). Numbers in the table represent patients at risk at each time point.
Figure 5. Renal survival in nephrotic patients who attain remission (P = 0.61). CS (), classic lesion; CL (), cellular lesion; TL (•), tip lesion. Numbers in the table represent patients at risk at each time point.
Figure 6. Renal survival in nephrotic patients who did not attain remission. P = 0.002 by the log-rank test. CS (), classic lesion; CL (), cellular lesion; TL (•), tip lesion. Numbers in the table represent patients at risk at each time point.
We reviewed the presentation and clinical course of nephroticadults with primary FSGS to determine the significance of theclassic scar and the cellular and the tip lesions. We concludethat there was no significant difference in the response tosteroid treatment among the three groups, with a remission rateof >50% in all patients who received steroid therapy. Inpatients who entered remission, we continue to observe a significantlyimproved renal survival compared with patients who did not enterremission, irrespective of the histologic lesion. However, therenal survival among nephrotic patients who did not enter remissionwas significantly poorer for patients with cellular and tiplesions compared with patients with classic scars. Thus, innephrotic adults with primary FSGS, the response to therapyremains the best prognostic indicator of outcome irrespectiveof the histologic subclassification.
In 1985, Schwartz and Lewis (18) recognized that patients withthe cellular lesion had more severe proteinuria and were moreoften nephrotic at presentation than patients with classic segmentalscars. Shortly after this, Weiss et al. (20), Detwiler et al.(13), and Valeri et al. (17) reported their experience in patientswith an identical pathologic lesion but chose the term "collapsing"FSGS, thus emphasizing the microvascular rather than the glomerularepithelial cell features of the lesion. They confirmed thatpatients with this lesion had more severe proteinuria than patientswith classic lesions; in addition, they found that the lesionwas more commonly seen in black individuals and was associatedwith a poor prognosis with more rapid progression to ESRD comparedwith patients with classic scars. As pointed out by Meyrier(12,19), although the nomenclature differs among the variousreports, the histologic features of the "cellular" and "collapsing"lesions of FSGS are identical.
Our present study confirms our original observations, whichis in contrast to the experience of Detwiler et al. (13) andValeri et al. (17), who found remission rates of <20% andoverall progression to ESRD in 50% of patients over 2 to 3 yr.The reason for the poorer response rate in these studies isnot clear but may be due to differences in therapeutic approachand to the presence of more advanced renal disease as the levelof renal insufficiency and degree of tubulointerstitial injurywere greater and the involvement with cellular lesions was morewidespread in the experience of Detwiler et al. (13) and Valeriet al. (17) compared with our patients. Consistent with thishypothesis is our observation that remission rates were significantlyworse in patients with 20% cellular lesions. Thus, early recognitionand treatment of patients with the cellular lesion may improveboth the likelihood of a therapeutic response and the prognosis.
Initial reports in nephrotic patients with the tip lesion suggestedan excellent response to steroids and favorable course similarto that of minimal-change disease rather than FSGS (14,21,23,24).Subsequent reports found that the response and course in patientswith the tip lesion was similar to that of patients with FSGSand thus questioned the clinical significance of this feature(6,10,25,26). In 1985, Howie et al. (14) reported the clinicalcourse in 31 patients with the tip lesion. They found that 48%of patients attained remission with steroids, and this resultedin an excellent prognosis with a 10-yr renal survival of 90%.However, in the 52% of patients who were unresponsive to treatment,the 10-yr renal survival was 30%. Thus, their experience withthe tip lesion was similar to that reported in patients withclassic FSGS. Recently, however, Stokes et al. (27) publishedtheir experience in 29 patients with he tip lesion, in whomthey found the presentation and course more similar to thatof minimal-change disease than FSGS. Patients with the tip lesionhad a sudden onset of the nephrotic syndrome with the time frompresentation to biopsy of 2.4 mo and an overall remission rateof 72% with a complete remission rate of 58%. Of the eight patientswho did not attain remission, only one progressed to ESRD; however,the follow-up was only 21.6 mo overall. Our experience withthe presentation and response to treatment in patients withthe tip lesion reflects that of Stokes et al. (27). However,unlike Stokes et al., we found that the prognosis in patientswho did not attain remission remains poor (with an overall follow-upof 99 mo), similar to that of FSGS rather than minimal-changedisease. Finally, it is of interest that Stokes et al. (27)found that 74% of patients with the tip lesion had coexistingsegmental lesions that would preclude a diagnosis of minimal-changedisease. Thus, although the prognosis is good for patients withthe tip lesion given their high rate of response to therapy,the question of whether the tip lesion should be considereda variant of minimal-change disease rather than FSGS remainsunresolved.
The best predictor of outcome in nephrotic patients with primaryFSGS, irrespective of histologic variant, is a remission inproteinuria (1,4,5,16,28). Because spontaneous remissions arerare and the use of conservative management alone rarely leadsto remission in nephrotic patients with FSGS, a trial of steroidshas been recommended (2–5). In cases in which there isconcern regarding the use of steroids as initial therapy, suchas the obese patient or patients with diabetes, the use of cyclosporinemay be a beneficial alternative, but it also has risk (1,29–31).Previous attempts to determine which patients are most likelyto benefit from a trial of therapy have failed to demonstrateany clinical or histologic features at biopsy that reliablypredict response (3,5,16). Recently, Bazzi et al. (32) showedthat the fractional excretion of IgG, a measure of protein selectivity,is highly predictive of response to steroid and immunosuppressivetherapy in their patients with FSGS. This observation must beconfirmed in larger numbers of patients with primary FSGS (includingthe histologic variants). Until then, patients who have primaryFSGS and remain nephrotic despite conservative treatment shouldreceive a trial of steroids or immunosuppressive therapy.
Acknowledgments
Results of this study were presented at the 35th Annual Meetingof the American Society of Nephrology, October 2002 in Philadelphia,PA.
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Received for publication April 14, 2004.
Accepted for publication May 29, 2004.
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[Abstract][Full Text][PDF]
M. Albaqumi, T. J. Soos, L. Barisoni, and P. J. Nelson Collapsing Glomerulopathy
J. Am. Soc. Nephrol.,
October 1, 2006;
17(10):
2854 - 2863.
[Abstract][Full Text][PDF]
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Abstract
Introduction
5 mg/dl or the need for renal replacement therapy. The level of proteinuria at the time of biopsy was categorized as (1) nephrotic-range proteinuria defined as >3 g/d protein and (2) massive proteinuria defined as >10 g/d protein. Nephrotic syndrome was defined as nephrotic-range proteinuria and hypoalbuminemia (
3.5 g/dl). Hypertension was defined as a systolic BP >140 mmHg and a diastolic BP >90 mmHg. In patients with nephrotic proteinuria, complete remission was defined as a urine protein of 
2 test. Mann-Whitney and ANOVA using Dunn multiple comparison tests were used for evaluating the continuous data. Renal survival time from the date of biopsy to ESRD was determined by product-limit life-table distributions and compared using a log-rank test. Data are reported as a mean ± SD. P < 0.05 is considered significant. 
. There were no significant differences among the groups in the clinical features at biopsy in treated patients (Table 4). The degree of interstitial fibrosis and global sclerosis was similar among the groups, but the proportion of glomeruli with classic segmental scars was highest in patients with classic FSGS, and patients with cellular FSGS had a greater proportion of glomeruli with any glomerular lesion compared with patients with tip lesions (Table 5). 
). The involved capillaries are occluded by foamy macrophages, and the uninvolved glomerulus has patent capillaries and normal mesangial matrix and cellularity. Hilar arterioles (*). Magnification, x66, PAS stain.
), classic lesion; CL (
), cellular lesion; TL (•), tip lesion. Numbers in the table represent patients at risk at each time point.