Skip to main content

Main menu

  • Home
  • Content
    • Published Ahead of Print
    • Current Issue
    • Podcasts
    • Subject Collections
    • Archives
    • Kidney Week Abstracts
    • Saved Searches
  • Authors
    • Submit a Manuscript
    • Author Resources
  • Trainees
    • Peer Review Program
    • Prize Competition
  • About CJASN
    • About CJASN
    • Editorial Team
    • CJASN Impact
    • CJASN Recognitions
  • More
    • Alerts
    • Advertising
    • Feedback
    • Reprint Information
    • Subscriptions
  • ASN Kidney News
  • Other
    • ASN Publications
    • JASN
    • Kidney360
    • Kidney News Online
    • American Society of Nephrology

User menu

  • Subscribe
  • My alerts
  • Log in
  • Log out
  • My Cart

Search

  • Advanced search
American Society of Nephrology
  • Other
    • ASN Publications
    • JASN
    • Kidney360
    • Kidney News Online
    • American Society of Nephrology
  • Subscribe
  • My alerts
  • Log in
  • Log out
  • My Cart
Advertisement
American Society of Nephrology

Advanced Search

  • Home
  • Content
    • Published Ahead of Print
    • Current Issue
    • Podcasts
    • Subject Collections
    • Archives
    • Kidney Week Abstracts
    • Saved Searches
  • Authors
    • Submit a Manuscript
    • Author Resources
  • Trainees
    • Peer Review Program
    • Prize Competition
  • About CJASN
    • About CJASN
    • Editorial Team
    • CJASN Impact
    • CJASN Recognitions
  • More
    • Alerts
    • Advertising
    • Feedback
    • Reprint Information
    • Subscriptions
  • ASN Kidney News
  • Visit ASN on Facebook
  • Follow CJASN on Twitter
  • CJASN RSS
  • Community Forum
Original ArticlesClinical Immunology and Pathology
You have accessRestricted Access

Collapsing Glomerulopathy in 19 Patients with Systemic Lupus Erythematosus or Lupus-Like Disease

Steven P. Salvatore, Laura M. C. Barisoni, Andrew M. Herzenberg, Praveen N. Chander, Volker Nickeleit and Surya V. Seshan
CJASN June 2012, 7 (6) 914-925; DOI: https://doi.org/10.2215/CJN.11751111
Steven P. Salvatore
*Department of Pathology, Weill Cornell Medical College, New York, New York;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Laura M. C. Barisoni
†Department of Pathology, New York University Medical Center, New York, New York;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrew M. Herzenberg
‡Department of Pathology, University of Toronto, Toronto, Canada;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Praveen N. Chander
§Department of Pathology, New York Medical College, Valhalla, New York; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Volker Nickeleit
‖Department of Pathology, University of North Carolina School of Medicine, Chapel Hill, North Carolina
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Surya V. Seshan
*Department of Pathology, Weill Cornell Medical College, New York, New York;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data Supps
  • Info & Metrics
  • View PDF
Loading

Summary

Background and objectives Collapsing glomerulopathy is a podocytopathy with segmental or global wrinkling and collapse of capillary walls and overlying epithelial cell proliferation. Idiopathic collapsing glomerulopathy is a distinct clinicopathologic entity with significant proteinuria, poor response to immunosuppressive therapy, and rapid progression to renal failure. Collapsing glomerulopathy is associated with viral infections, autoimmune disease, and drugs. This work presents the largest group of collapsing glomerulopathy in patients with SLE.

Design, setting, participants, & measurements Clinicopathological features were retrospectively studied in 19 patients with SLE (16 patients) or SLE-like (3 patients) disease with collapsing glomerulopathy.

Results Initially, 95% of patients had nephrotic syndrome with proteinuria of 3–12 g per 24 hours, creatinine levels of 0.6–9.6 mg/dl, positive lupus serologies, and normal complement levels in 63%. Segmental and/or global collapsing glomerulopathy was seen in 11%–77% of glomeruli. Tubular atrophy with focal microcystic changes and interstitial fibrosis was seen in 35% of patients. Minimal glomerular mesangial deposits were noted in 63% of patients, and extensive foot process effacement was seen in 82% of patients. Initial treatment was with pulse/oral steroids. Follow-up from 13 patients revealed that 7 patients progressed to ESRD at the time of biopsy up to 21 months later, 1 patient returned to normal creatinine (1.1 mg/dl) without proteinuria, and 5 patients had creatinine of 1.2–3.6 mg/dl with proteinuria of 0.37–4 g per 24 hours.

Conclusions Collapsing glomerulopathy may be seen in SLE patients presenting with massive proteinuria with or without lupus nephritis, which may have prognostic significance.

Introduction

Collapsing glomerulopathy (CG) has become an increasingly recognized pattern of glomerular injury with a rapid clinical course including massive proteinuria and relative resistance to standard treatment. The pathologic appearance is characterized by global or segmental collapse of the glomerular capillary tuft, with wrinkling and retraction of the capillary walls overlaid by epithelial cell proliferation in the Bowman space that is frequently accompanied by tubulointerstitial disease (1–3). CG is regarded as a podocytopathy, it is predominantly seen in the primary form in patients of African descent, and it has been associated with numerous etiologies, including viral infections (HIV, cytomegalovirus, Parvovirus B19, and hepatitis C virus), drugs (pamidronate and all forms of IFN), and anecdotally, autoimmune diseases (SLE and mixed connective tissue disease) (4,5). The trigger for the development of CG has been elusive, but an underlying immune-mediated mechanism has been postulated in most cases.

Podocytes have a characteristic phenotype in the adult glomerulus, expressing transcription factor Wilms’ tumor protein 1 (WT-1) as well as podocyte proteins podocin, synaptopodin, podocalyxin, nephrin, and glomerular epithelial protein 1 (6). According to the dysregulated podocyte phenotype theory, in CG, the affected podocytes lose markers of differentiation (WT-1, glomerular epithelial protein 1, synaptopodin, and podocalyxin) and assume a proliferative dedifferentiated state that is positive for Ki-67 and paired box gene 2 (7). However, the renopoietic hypothesis suggests that the lack of maturity markers is because of the absence of podocytes and participation of progenitor cells migrating from the Bowman capsule to form the proliferative lesions in the urinary space (pseudocrescents) (7,8).

Anecdotal CG in autoimmune diseases including SLE, SLE-like disease, and mixed connective tissue disease has been previously reported (1,2,9–18). The aim of this study is to report an analysis of the clinicopathologic findings and the possible association of renal lesions with CG in the setting of SLE and lupus-like disease and review the literature of the reported cases.

Materials and Methods

Native renal biopsies, processed using standard techniques for light, immunofluorescence, and electron microscopy, from 2003 to 2010 were reviewed from patients with history of SLE or SLE-like disease and a diagnosis of CG. SLE-like disease was defined as having multiple lupus criteria suggesting but not meeting the total of four criteria required for American Rheumatology Association (ARA) diagnosis of SLE (19). Demographic, clinical, laboratory, and serologic findings were obtained. The diagnosis of CG was made using the Columbia Classification criteria for the collapsing variant of FSGS (3), which are based on light microscopy showing at least one glomerulus with global or segmental collapse of the capillary tuft, wrinkling of the glomerular basement membrane, and hyperplasia and/or hypertrophy of the overlying epithelial cells usually containing intracytoplasmic protein droplets and vacuolization (3). The light, immunofluorescence, and electron microscopic findings are summarized.

Immunohistochemical stains on paraffin-embedded sections in 14 of 19 cases were performed using the Bond Max Autostainer (Leica Microsystems, IL) to further characterize the glomerular lesions. The primary antibodies used were against Ki-67 (clone MIB-1; Dako), mouse monoclonal antibody against β-dystroglycan (1:50 dilution, clone 43DAG1/8D5; NovoCastra), mouse monoclonal antibody against synaptopodin (1:10 dilution, clone G1D4; Progen Biotechnik), rabbit anti-human podocin (20 μg/ml dilution, clone PODO 11-A, Alpha Diagnostics), and polyclonal antiserum against WT-1 (C19; Santa Cruz Biotechnology). The sections were deparaffinized, and endogenous peroxidase was inactivated. Antigen retrieval was accomplished using the Bond Epitope Retrieval Solution 2 at 99–100°C for 20 minutes (Leica Microsystems). The sections were then incubated sequentially with the primary antibody for 25 minutes, the post-primary antibody for 15 minutes, and the polymer for 25 minutes, ending with colorimetric development with diaminobenzidine for 10 minutes (Bond Polymer Define Detection; Leica Microsystems).

This study was approved by the Institutional Review Board of Weill Cornell Medical College, New York. Patient informed consent was not required by the Institutional Review Board, because the study was a retrospective review of clinical and archived pathologic material only.

Results

Clinical and laboratory characteristics from the 19 patients are listed in Table 1. The patients ranged in age from 16 to 65 years old, and they were predominantly of African descent (17 of 19 patients; 89%) and female (male to female ratio is 4:15). SLE or lupus nephritis was diagnosed before the onset of CG in 11 patients (1–20 years before CG presentation), whereas a simultaneous first-time diagnosis of SLE along with CG occurred in 8 patients. At the time of renal biopsy, 16 of 19 patients had active lupus or lupus-like disease by clinical symptoms, including rash (4), arthritis (6), mucositis (2), antinuclear antibody (ANA) positive with or without double-stranded DNA (dsDNA) (13), and hypocomplementemia (8). The median serum Cr and BUN at presentation were elevated (3.0 mg/dl, interquartile range [IQR]=3.3 mg/dl and 31.5 mg/dl, IQR=22 mg/dl, respectively). The proteinuria ranged from 0.3 to 12 g per 24 hours, with a median of 6 g per 24 hours (IQR=5.6 g per 24 hours). All patients but one (case #19) had nephrotic range proteinuria at presentation. Complement levels were within the normal range in 10 cases; median C3 was 76 mg/dl (IQR=103 mg/dl, range=27–164), and median C4 was 11.8 mg/dl (IQR=33 mg/dl, range=8–61). ANA was positive in 14 of 15 (93%) patients. The remaining four patients had previously diagnosed SLE and did not have a current ANA titer on record. Anti-dsDNA was positive in 12 of 15 (80%) tested patients. All patients were HIV-negative. hepatitis C virus (n=11) and Parvovirus (n=7) serologies were negative in patients tested.

View this table:
  • View inline
  • View popup
Table 1.

Clinical and laboratory findings at the time of biopsy

The pathologic findings are listed in Table 2. At least one glomerulus in each biopsy displayed either segmental or global collapse accompanied by epithelial proliferation (Figure 1, A and B). Global collapse was seen in up to a maximum of 65% of glomeruli per biopsy (mean=21.1%). Segmental collapse was present in 0%–48% of glomeruli per biopsy. However, 68% had a focal distribution (involvement of <50% of glomeruli). Global glomerulosclerosis was present in 11 of 19 biopsies, ranging from 0% to 57% of the total glomeruli. Acute tubular injury was seen in 11 of 19 cases, ranging from focal to extensive. Tubular atrophy and interstitial fibrosis varied from <5% to 90% of the renal cortical areas, and tubular microcyst formation was observed in 7 of 19 patients (Figure 1, C and D); 6 of 19 cases disclosed moderate arterio- and arteriolosclerosis, and the rest of the cases had no significant to mild vascular changes, with the exception of antiphospholipid-associated thrombotic microangiopathy in one case (case #16). No evidence of lupus vasculitis or vasculopathy was noted. Morphologic changes of lupus nephritis (LN) were present in seven cases, ranging from mesangial hypercellularity in four cases to focal endocapillary proliferation in one case, which corresponded to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classes II and III LN (Figure 2, A and B). One case had capillary wall thickening with diffuse subendothelial deposits without endocapillary proliferation (ISN/RPS class IV LN) (Figure 2C). Two cases displayed small external capillary wall spike formation, which is seen best by Jones methenamine silver staining, corresponding to ISN/RPS class V LN (Figure 2D). No necrosis or crescent formation was seen in any of the biopsies.

View this table:
  • View inline
  • View popup
Table 2.

Renal pathologic findings

Figure 1.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 1.

Glomerular and tubulointerstitial findings in collapsing glomerulopathy in the setting of SLE. Pathologic features of segmental (A) and/or global (B) collapsing glomerulopathy with capillary wrinkling and retraction and epithelial cell proliferation containing prominent protein resorption droplets. Tubular microcysts and chronic interstitial disease (C) and tubular epithelial cell injury (D) were also seen. A, Jones methenamine silver; B, Jones methenamine silver; C, Periodic acid-Schiff; D, hematoxylin & eosin. Original magnification, ×600 in A; ×400 in B; ×200 in C; ×200 in D.

Figure 2.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 2.

Lupus glomerulonephritis was present in 8 of 19 cases. (A) Mesangial (class II) in four cases. (B) Focal proliferative (class III) in one case. (C) Diffuse lupus nephritis (class IV) in one case with diffuse subendothelial deposits detected by electron microscopy. (D) Membranous (class V) in two cases. Small capillary wall spikes are indicated by the white arrow. A, periodic acid-Schiff; B, periodic acid-Schiff; C, Jones methenamine silver; D, Jones methenamine silver. Original magnification, ×400 in A; ×600 in B; ×600 in C; ×600 in D.

There was positive immunofluorescence staining for immune deposits in 84% of the cases (16 of 19 cases) (Figure 3, A and B). Where present, the deposits were commonly trace to 1+ in mesangial locations for various combinations of immunoglobulins, complement components (C3, C1q), and κ- and λ-light chains. Glomerular immune complex deposits were found by electron microscopy in eight cases: four cases with mesangial deposits (Figure 3C), two cases with subendothelial deposits, and two cases with subepithelial deposits. The foot processes were affected in all cases, ranging from 10% (two cases) to 100% effacement (Figure 3D). Four cases displayed endothelial cell tubuloreticular inclusions.

Figure 3.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 3.

Immunoflourescence and electron microscopic findings. Glomeruli in 16 of 19 cases displayed immune complex deposits by immunofluorescence (A; anti-IgG). The remaining cases were negative by immunofluorescence (B; anti-IgG). Mainly mesangial (eight cases) lupus nephritis with mesangial electron-dense deposits (C; electron microscopy) were seen. Eleven cases showed only wrinkling and retraction of the glomerular basement membranes without immune complex deposits by electron microscopy (D). Original magnification, ×400 in A; ×400 in B; ×6000 in C; ×6000 in D.

Immunohistochemical stains for podocyte proteins have been documented in idiopathic CG and HIV-associated nephropathy (HIVAN) but not CG associated with autoimmune disease (20). Previous reports indicate widespread loss of synaptopodin and WT-1 markers in viral and idiopathic related CG with less dysregulation and dedifferentiation in reactive and genetic cases (20). In this study, WT-1 staining was preserved in 9 of 14 cases (64%), with loss of synaptopodin and podocin in the collapsed segments in 10 of 12 (83%) cases and 8 of 10 (80%) cases, respectively (Figure 4, A–C and Table 2). β-Dystroglycan was absent in 7 of 11 (63%) cases in the collapsed areas (Figure 4D). Ki-67 proliferation marker showed nuclear positivity in proliferating glomerular epithelial cells overlying the collapse in all cases tested (13) (Figure 4E).

Figure 4.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 4.

Immunohistochemical staining for podocyte antigens and Ki-67 labeling in collapsed glomeruli. The glomeruli with collapsing lesions largely displayed preservation for Wilms’ tumor protein 1 staining (A), with decrease or loss in the collapsed regions for synaptopodin (B) and podocin (C). Anchoring protein β-dystroglycan was lost or attenuated in the collapsed regions (D). Proliferation marker (Ki-67) was positive in epithelial cell nuclei in all cases (E). Original magnification, ×600 (immunohistochemistry).

Follow-up data were available for 13 patients from 2 months to 3.5 years (Table 3); 7 of 13 (54%) patients progressed to ESRD from the time of biopsy to 21 months after presentation despite treatment. One case (8) was rebiopsied at 10 months for rapidly rising Cr to 11 mg/dl and showed persistent collapsing features and increased interstitial fibrosis with microcystic changes; this case was in ESRD. A second case with partial response (14) was rebiopsied at 1 year for persistent proteinuria (5–6 g) and showed increased segmental and global glomerulosclerosis with partial foot process effacement (40%) and advancing interstitial fibrosis. The treatment was most typically comprised of pulse dose steroids (12 of 13 cases); six cases received additional mycophenolate mofetil, one case received intravenous Igs, one case received azathioprine, and two cases received plaquenil. Of the six patients who did not progress to ESRD, one patient achieved return to normal Cr, and four patients had Cr levels between 1.2 and 3.6 mg/dl at last follow-up. In those patients with partial response, treatment consisted of high-dose, long-term oral steroids ranging from 60 to 100 mg/d for 2–6 months. The partial and complete responders had fewer collapsing lesions (31% versus 42%), less global glomerulosclerosis (8% versus 22%), and less interstitial fibrosis (28% versus 49%). In addition, a better response was seen in patients with concomitant LN. Four of six responders had LN, whereas only one of seven of those cases progressing to ESRD had LN (case #17).

View this table:
  • View inline
  • View popup
Table 3.

Initial treatment and follow-up data

Discussion

Herein, we report a cohort of patients presenting with SLE or SLE-like disease, nephrotic syndrome, or nephrotic range proteinuria and renal insufficiency, with an active lupus flare (16 of 19 patients; 84%) and biopsy-proven CG. Underlying immune complex-mediated LN was also noted in 8 of 19 cases, which ranged from mesangial (class II) in four cases, focal proliferative (class III) in one case, and diffuse proliferative (class IV) in one case to membranous (class V) in two cases; 11 of the patients had SLE from 1 to 20 years before the diagnosis of CG, whereas eight patients had simultaneous new diagnosis of SLE and onset of CG. In the majority of cases, treatment was initiated with high doses of steroids for prolonged periods, with 6 of 13 cases achieving complete (1 case) or partial (5 case) remission.

This report represents, to our knowledge, the largest collection of cases with biopsy-proven CG in the setting of SLE or SLE-like disease with clinicopathological data and follow-up information. Our findings are similar to previous anecdotal case reports (Table 4) (9–13,15–18). Overall, 13 patients with ARA criteria meeting SLE and 9 other SLE-like patients have been reported as well as 5 additional patients presenting with isolated positive serology for ANA but lacking other SLE symptoms, a finding of unclear significance (1,2,9–18,21). In both the present and previously reported cases, the patients are predominantly female and of African descent with nephrotic range proteinuria, positive ANA, and relatively poor response to treatment. In larger studies of CG (1,2,21), eight additional cases of SLE, SLE-like, or mixed connective tissue disease were briefly described without specific clinical or outcome data available. All these patients had positive ANA, four patients had positive dsDNA, one patient had hypocomplementemia, and one patient had endothelial tubuloreticular inclusions on electron microscopy. A series of podocytopathy in SLE also contained two patients with CG and SLE, one of which progressed to ESRD and died secondary to sepsis (14).

View this table:
  • View inline
  • View popup
Table 4.

Literature review of collapsing glomerulopathy in lupus or lupus-like conditions

Follow-up information was provided in eight of the reported cases: four cases had partial remission, two cases had a complete remission, and two cases led to no response or death during therapy (9–12,15–18). Only 25% progression to ESRD or death in this group is a surprising finding, and it may be related to a shorter follow-up period or less-stringent criteria for the diagnosis of CG. In fact, all previously reported cases of remission had either diffuse proliferative LN (5) or thrombotic microangiopathy in the biopsy, which may confuse the diagnosis.

CG has been associated with a variety of etiologies, including the well-recognized glomerular and tubulointerstitial lesions in HIV infection or Parvovirus B19 (22–24). CG is also described secondary to certain medications, including Pamidronate (25), and with all forms of IFN (α, β, and γ) therapy (5).

One common theme to both HIVAN and the various etiologies of HIV-negative CG seems to be a perturbation of the immune system, whether triggered by an infectious agent or an endogenous autoimmune T cell regulatory disruption (26). A T cell cytokine-mediated process modified by genetic influences has been proposed as one of the underlying mechanisms inducing SLE (27). T cells are abnormal in SLE, expressing lower levels of CD3ζ and IL2 and having a diminished cytotoxic activity, a lower proportion of T regulatory cells, and a faster homing response to chemokines such as CXCL12 (28). In addition, patients with SLE have previously been reported to develop proteinuric podocytopathic renal disease in the form of FSGS (29,30) or minimal change disease, which some have suggested to result from mainly T cell activation (31,32). Although the pathophysiology of the podocyte injury in SLE is not entirely clear, an immune-mediated pathway through an antibody- or T cell-mediated process is a possible mechanism in the setting of a genetically susceptible patient population.

How does the autoimmune injury occurring in SLE contribute to podocyte injury, and are they necessarily related to one another? In our patients, the time of onset of CG seems to indicate that active lupus disease was associated with the development of CG, which was supported by serologic and clinical parameters. Humoral factors may play a role in inducing podocyte injury, which was shown in the work by Avila-Casado et al. (33); rats injected with serum from patients with CG developed proteinuria, whereas rats injected with FSGS or normal human serum did not. Other mouse models have shown that an antibody-induced glomerular injury produced a CG-like pattern in three different strains of transgenic mice (34–36). A circulating factor has been postulated to play a role in podocyte injury in FSGS not otherwise specified in the form of high soluble urokinase receptor (37). In a recent report by El Karoui et al. (38), IgA nephropathy was associated with podocyte injury representing all variants of FSGS, including the collapsing variant. The work by El Karoui et al. (38) concluded that immunologic injury may be responsible for the epithelial injury seen in immune complex-mediated glomerular disease. Development of antiphospholipid antibodies and subsequent thrombotic microangiopathy may also play a role in some lupus patients by causing podocyte ischemia to contribute to epithelial injury (particularly case #16 in our study).

Whether by a T cell-mediated or humoral process, the podocytes (all cases) and the tubular epithelial cells (12 cases) seem to be affected with a change in functional, morphologic, and immunophenotypic features. By immunohistochemistry, the glomerular epithelial cells show a proliferative (100% of cases with +Ki-67 labeling) and dedifferentiated phenotype, displaying loss of synaptopodin and podocin localized mainly in the areas of CG in 83% and 80% of cases tested, respectively, whereas WT-1 preservation is seen in 64% of the cases. The pattern of staining for synaptopodin and podocin is consistent with other nonlupus-related cases of idiopathic CG or HIVAN (20), but WT-1 preservation seems to be unique to an autoimmune etiology, because idiopathic cases of CG typically also show a loss of WT-1 (20). WT-1 positivity in CG cases with SLE was also noted in one other reported case (18).

Because the majority of patients with both HIVAN and idiopathic CG are of African descent, there is an increased probability of a genetic susceptibility to developing this type of proliferative podocyte disease (1,2,21,39–44). The work by Freedman et al. (45) found a 5.4-fold increase in ESRD among HIV-negative first- and second-degree relatives of patients with known HIVAN, strengthening the notion of a genetically encoded susceptibility to kidney injury. Studies by Kopp et al. (46) and subsequently, Genovese et al. (47) found an association of FSGS and nondiabetic kidney disease in African-Americans with the MYH9 and closely positioned APOL1 genes on chromosome 22.

SLE occurs in African-American women four times more frequently than Caucasians (48). CG is also highly associated with an African lineage (1,2,21). Our study also shows that there is both a strong African and female preponderance, which may suggest a coincidental association between the two diseases in a patient population that is at a higher risk of developing both conditions. At all institutions included in the study, biopsies of SLE patients are more frequently from women than men. Previous studies of nonlupus nephritides developing in patients with SLE have shown that the association with SLE and podocyte injury, including minimal change disease and FSGS, has been far higher in patients with SLE (1.6% and 1.7%, respectively) than in the general population (<0.01%), suggesting a noncoincidental link (10,14,30). The multifactorial interplay between ethnic background, presence of SLE, and development of CG in these patients is not currently known, and the main aim of this multicenter study is to bring this rare disease process to the attention of clinicians and pathologists as yet another renal lesion in SLE patients that may require a different management.

Owing to the rarity of this disease, the study has a few limitations. This study is the largest to date on CG in SLE, which required the collective efforts of five large renal biopsy centers to amass the 19 total cases. Sampling bias may be present based on the tertiary centers involved. The retrospective and small series comprised a heterogeneous group of patients with uncontrolled comorbidities, who received varying treatment regimens and had inconsistent follow-up periods.

In summary, SLE patients with massive proteinuria and rapidly progressive renal failure may have renal injury not related to classic immune complex-mediated LN but as a result of a podocytopathy, such as CG. The emerging association between CG and SLE should be recognized for additional characterization. Therefore, kidney biopsy is useful for the definitive diagnosis and findings of prognostic value in these patients.

Disclosures

None.

Acknowledgments

The authors thank Drs. Satish Arora, James Chevalier, Vanita Jassal, Odler Jeanlouie, Valerie Johnson, Joshua Kaplan, Kyriakos Kirou, Kameswari Lakshmi, C. Bruce Murdock, James Najarian, Kotresha Neelakantappa, Chike Okechukwu, Rodolfo Ortiz, Eduardo Perelstein, Alluru Reddi, Nathan Thompson, Kevin Vitting, Joseph Weisstuch, and Joan Wither for providing the clinical information.

This study was presented in part at the American Society of Nephrology Renal Week, November 16–21, 2010, Denver, Colorado.

Footnotes

  • Published online ahead of print. Publication date available at www.cjasn.org.

  • See related editorial, “Collapsing Glomerulopathy in Systemic Lupus Erythematosus: An Extreme Form of Lupus Podocytopathy?,” on pages 878–880.

  • Received November 18, 2011.
  • Accepted March 6, 2012.
  • Copyright © 2012 by the American Society of Nephrology

References

  1. ↵
    1. Valeri A,
    2. Barisoni L,
    3. Appel GB,
    4. Seigle R,
    5. D’Agati V
    : Idiopathic collapsing focal segmental glomerulosclerosis: A clinicopathologic study. Kidney Int 50: 1734–1746, 1996pmid:8914044
    OpenUrlCrossRefPubMed
  2. ↵
    1. Laurinavicius A,
    2. Hurwitz S,
    3. Rennke HG
    : Collapsing glomerulopathy in HIV and non-HIV patients: A clinicopathological and follow-up study. Kidney Int 56: 2203–2213, 1999pmid:10594796
    OpenUrlCrossRefPubMed
  3. ↵
    1. D’Agati VD,
    2. Fogo AB,
    3. Bruijn JA,
    4. Jennette JC
    : Pathologic classification of focal segmental glomerulosclerosis: A working proposal. Am J Kidney Dis 43: 368–382, 2004pmid:14750104
    OpenUrlCrossRefPubMed
  4. ↵
    1. Albaqumi M,
    2. Soos TJ,
    3. Barisoni L,
    4. Nelson PJ
    : Collapsing glomerulopathy. J Am Soc Nephrol 17: 2854–2863, 2006pmid:16914539
    OpenUrlAbstract/FREE Full Text
  5. ↵
    1. Markowitz GS,
    2. Nasr SH,
    3. Stokes MB,
    4. D’Agati VD
    : Treatment with IFN-alpha, -beta, or -gamma is associated with collapsing focal segmental glomerulosclerosis. Clin J Am Soc Nephrol 5: 607–615, 2010pmid:20203164
    OpenUrlAbstract/FREE Full Text
  6. ↵
    1. Bariety J,
    2. Mandet C,
    3. Hill GS,
    4. Bruneval P
    : Parietal podocytes in normal human glomeruli. J Am Soc Nephrol 17: 2770–2780, 2006pmid:16943305
    OpenUrlAbstract/FREE Full Text
  7. ↵
    1. Barisoni L,
    2. Kriz W,
    3. Mundel P,
    4. D’Agati V
    : The dysregulated podocyte phenotype: A novel concept in the pathogenesis of collapsing idiopathic focal segmental glomerulosclerosis and HIV-associated nephropathy. J Am Soc Nephrol 10: 51–61, 1999pmid:9890309
    OpenUrlAbstract/FREE Full Text
  8. ↵
    1. Smeets B,
    2. Uhlig S,
    3. Fuss A,
    4. Mooren F,
    5. Wetzels JFM,
    6. Floege J,
    7. Moeller MJ
    : Tracing the origin of glomerular extracapillary lesions from parietal epithelial cells. J Am Soc Nephrol 20: 2604–2615, 2009pmid:19917779
    OpenUrlAbstract/FREE Full Text
  9. ↵
    1. Marques LP,
    2. Pacheco GG,
    3. Rioja LS,
    4. Nunes SN,
    5. Velone ST,
    6. Santos OR
    : Can systemic lupus erythematosus be the cause of collapsing glomerulopathy? Lupus 14: 853–855, 2005pmid:16302682
    OpenUrlCrossRefPubMed
  10. ↵
    1. Hertig A,
    2. Droz D,
    3. Lesavre P,
    4. Grünfeld J-P,
    5. Rieu P
    : SLE and idiopathic nephrotic syndrome: Coincidence or not? Am J Kidney Dis 40: 1179–1184, 2002pmid:12460036
    OpenUrlCrossRefPubMed
    1. Amoura Z,
    2. Georgin-Lavialle S,
    3. Haroche J,
    4. Merrien D,
    5. Brocheriou I,
    6. Beaufils H,
    7. Piette J-C
    : Collapsing glomerulopathy in systemic autoimmune disorders: A case occurring in the course of full blown systemic lupus erythematosus. Ann Rheum Dis 65: 277–278, 2006pmid:16410539
    OpenUrlFREE Full Text
  11. ↵
    1. Arbel O,
    2. Pizov G,
    3. Ben-Yehuda A,
    4. Rubinow A,
    5. Naparstek Y,
    6. Amital H
    : Hyperacute renal failure as the initial presentation of systemic lupus erythematosus. Lupus 14: 331–333, 2005pmid:15864922
    OpenUrlCrossRefPubMed
  12. ↵
    1. Avila-Casado MC,
    2. Vargas-Alarcon G,
    3. Soto ME,
    4. Hernandez G,
    5. Reyes PA,
    6. Herrera-Acosta J
    : Familial collapsing glomerulopathy: Clinical, pathological and immunogenetic features. Kidney Int 63: 233–239, 2003pmid:12472788
    OpenUrlCrossRefPubMed
  13. ↵
    1. Kraft SW,
    2. Schwartz MM,
    3. Korbet SM,
    4. Lewis EJ
    : Glomerular podocytopathy in patients with systemic lupus erythematosus. J Am Soc Nephrol 16: 175–179, 2005pmid:15548564
    OpenUrlAbstract/FREE Full Text
  14. ↵
    1. Melo NC,
    2. Malheiros DM,
    3. Barros RT,
    4. Woronik V
    : Collapsing glomerulopathy associated with proliferative lupus nephritis: Reversible acute kidney injury. Lupus 20: 98–101, 2011pmid:21078765
    OpenUrlCrossRefPubMed
    1. Rifkin SI,
    2. Gutta H,
    3. Nair R,
    4. McFarren C,
    5. Wheeler DE
    : Collapsing glomerulopathy in a patient with mixed connective tissue disease. Clin Nephrol 75[Suppl 1]: 32–36, 2011pmid:21269591
    OpenUrlPubMed
    1. Gupta R,
    2. Sharma A,
    3. Bhowmik D,
    4. Gupta S,
    5. Agarwal S,
    6. Gupta R,
    7. Dinda A
    : Collapsing glomerulopathy occurring in HIV-negative patients with systemic lupus erythematosus: Report of three cases and brief review of the literature. Lupus 20: 866–870, 2011pmid:21339242
    OpenUrlCrossRefPubMed
  15. ↵
    1. Tungekar MF,
    2. Waller S,
    3. Clothier JC
    : Collapsing glomerulopathy in a girl with systemic lupus erythematosus. Pediatr Nephrol 26: 809–813, 2011pmid:21279391
    OpenUrlCrossRefPubMed
  16. ↵
    1. Tan EM,
    2. Cohen AS,
    3. Fries JF,
    4. Masi AT,
    5. McShane DJ,
    6. Rothfield NF,
    7. Schaller JG,
    8. Talal N,
    9. Winchester RJ
    : The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25: 1271–1277, 1982pmid:7138600
    OpenUrlCrossRefPubMed
  17. ↵
    1. Albaqumi M,
    2. Barisoni L
    : Current views on collapsing glomerulopathy. J Am Soc Nephrol 19: 1276–1281, 2008pmid:18287560
    OpenUrlAbstract/FREE Full Text
  18. ↵
    1. Detwiler RK,
    2. Falk RJ,
    3. Hogan SL,
    4. Jennette JC
    : Collapsing glomerulopathy: A clinically and pathologically distinct variant of focal segmental glomerulosclerosis. Kidney Int 45: 1416–1424, 1994pmid:8072254
    OpenUrlCrossRefPubMed
  19. ↵
    1. Cohen AH,
    2. Sun NC,
    3. Shapshak P,
    4. Imagawa DT
    : Demonstration of human immunodeficiency virus in renal epithelium in HIV-associated nephropathy. Mod Pathol 2: 125–128, 1989pmid:2657719
    OpenUrlPubMed
    1. Kimmel PL,
    2. Ferreira-Centeno A,
    3. Farkas-Szallasi T,
    4. Abraham AA,
    5. Garrett CT
    : Viral DNA in microdissected renal biopsy tissue from HIV infected patients with nephrotic syndrome. Kidney Int 43: 1347–1352, 1993pmid:8315949
    OpenUrlCrossRefPubMed
  20. ↵
    1. Moudgil A,
    2. Nast CC,
    3. Bagga A,
    4. Wei L,
    5. Nurmamet A,
    6. Cohen AH,
    7. Jordan SC,
    8. Toyoda M
    : Association of parvovirus B19 infection with idiopathic collapsing glomerulopathy. Kidney Int 59: 2126–2133, 2001pmid:11380814
    OpenUrlCrossRefPubMed
  21. ↵
    1. Markowitz GS,
    2. Appel GB,
    3. Fine PL,
    4. Fenves AZ,
    5. Loon NR,
    6. Jagannath S,
    7. Kuhn JA,
    8. Dratch AD,
    9. D’Agati VD
    : Collapsing focal segmental glomerulosclerosis following treatment with high-dose pamidronate. J Am Soc Nephrol 12: 1164–1172, 2001pmid:11373339
    OpenUrlAbstract/FREE Full Text
  22. ↵
    1. Laurinavicius A,
    2. Rennke HG
    : Collapsing glomerulopathy—a new pattern of renal injury. Semin Diagn Pathol 19: 106–115, 2002pmid:12180632
    OpenUrlPubMed
  23. ↵
    1. Dayal AK,
    2. Kammer GM
    : The T cell enigma in lupus. Arthritis Rheum 39: 23–33, 1996pmid:8546735
    OpenUrlCrossRefPubMed
  24. ↵
    1. Lo M,
    2. Tsokos G
    : T cells in systemic lupus erythematosus: Progress toward targeted therapy. Rheumatologist Available online at www.the-rheumatologist.org/details/1311767/T_cells_in_Systemic_Lupus_Erythematosus.html. Accessed August 16, 2011
  25. ↵
    1. Hickman PL,
    2. Nolph KD,
    3. Jacobs R,
    4. Luger AM,
    5. Walker SE
    : Idiopathic focal segmental glomerulosclerosis in a patient with systemic lupus erythematosus: An unusual combination. Am J Kidney Dis 23: 582–586, 1994pmid:8154496
    OpenUrlPubMed
  26. ↵
    1. Baranowska-Daca E,
    2. Choi Y-J,
    3. Barrios R,
    4. Nassar G,
    5. Suki WN,
    6. Truong LD
    : Nonlupus nephritides in patients with systemic lupus erythematosus: A comprehensive clinicopathologic study and review of the literature. Hum Pathol 32: 1125–1135, 2001pmid:11679948
    OpenUrlCrossRefPubMed
  27. ↵
    1. Nishihara G,
    2. Nakamoto M,
    3. Yasunaga C,
    4. Takeda K,
    5. Matsuo K,
    6. Urabe M,
    7. Goya T,
    8. Sakemi T
    : Systemic lupus erythematosus in a patient with remitting minimal change nephrotic syndrome. Clin Nephrol 48: 327–330, 1997pmid:9403219
    OpenUrlPubMed
  28. ↵
    1. Dube GK,
    2. Markowitz GS,
    3. Radhakrishnan J,
    4. Appel GB,
    5. D’Agati VD
    : Minimal change disease in systemic lupus erythematosus. Clin Nephrol 57: 120–126, 2002pmid:11863121
    OpenUrlCrossRefPubMed
  29. ↵
    1. Avila-Casado MC,
    2. Perez-Torres I,
    3. Auron A,
    4. Soto V,
    5. Fortoul TI,
    6. Herrera-Acosta J
    : Proteinuria in rats induced by serum from patients with collapsing glomerulopathy. Kidney Int 66: 133–143, 2004pmid:15200420
    OpenUrlCrossRefPubMed
  30. ↵
    1. Smeets B,
    2. Te Loeke NAJM,
    3. Dijkman HBPM,
    4. Steenbergen MLM,
    5. Lensen JFM,
    6. Begieneman MPV,
    7. van Kuppevelt TH,
    8. Wetzels JFM,
    9. Steenbergen EJ
    : The parietal epithelial cell: a key player in the pathogenesis of focal segmental glomerulosclerosis in Thy-1.1 transgenic mice. J Am Soc Nephrol 15: 928–939, 2004pmid:15034095
    OpenUrlAbstract/FREE Full Text
    1. Kim Y-G,
    2. Alpers CE,
    3. Brugarolas J,
    4. Johnson RJ,
    5. Couser WG,
    6. Shankland SJ
    : The cyclin kinase inhibitor p21CIP1/WAF1 limits glomerular epithelial cell proliferation in experimental glomerulonephritis. Kidney Int 55: 2349–2361, 1999pmid:10354282
    OpenUrlCrossRefPubMed
  31. ↵
    1. Matsusaka T,
    2. Xin J,
    3. Niwa S,
    4. Kobayashi K,
    5. Akatsuka A,
    6. Hashizume H,
    7. Wang QC,
    8. Pastan I,
    9. Fogo AB,
    10. Ichikawa I
    : Genetic engineering of glomerular sclerosis in the mouse via control of onset and severity of podocyte-specific injury. J Am Soc Nephrol 16: 1013–1023, 2005pmid:15758046
    OpenUrlAbstract/FREE Full Text
  32. ↵
    1. Wei C,
    2. El Hindi S,
    3. Li J,
    4. Fornoni A,
    5. Goes N,
    6. Sageshima J,
    7. Maiguel D,
    8. Karumanchi SA,
    9. Yap H-K,
    10. Saleem M,
    11. Zhang Q,
    12. Nikolic B,
    13. Chaudhuri A,
    14. Daftarian P,
    15. Salido E,
    16. Torres A,
    17. Salifu M,
    18. Sarwal MM,
    19. Schaefer F,
    20. Morath C,
    21. Schwenger V,
    22. Zeier M,
    23. Gupta V,
    24. Roth D,
    25. Rastaldi MP,
    26. Burke G,
    27. Ruiz P,
    28. Reiser J
    : Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis. Nat Med 17: 952–960, 2011pmid:21804539
    OpenUrlCrossRefPubMed
  33. ↵
    1. El Karoui K,
    2. Hill GS,
    3. Karras A,
    4. Moulonguet L,
    5. Caudwell V,
    6. Loupy A,
    7. Bruneval P,
    8. Jacquot C,
    9. Nochy D
    : Focal segmental glomerulosclerosis plays a major role in the progression of IgA nephropathy. II. Light microscopic and clinical studies. Kidney Int 79: 643–654, 2011pmid:21178978
    OpenUrlCrossRefPubMed
  34. ↵
    1. Ray PE,
    2. Xu L,
    3. Rakusan T,
    4. Liu X-H
    : A 20-year history of childhood HIV-associated nephropathy. Pediatr Nephrol 19: 1075–1092, 2004pmid:15300477
    OpenUrlPubMed
    1. Ross MJ,
    2. Klotman PE
    : HIV-associated nephropathy. AIDS 18: 1089–1099, 2004pmid:15166524
    OpenUrlCrossRefPubMed
    1. Winston JA,
    2. Burns GC,
    3. Klotman PE
    : The human immunodeficiency virus (HIV) epidemic and HIV-associated nephropathy. Semin Nephrol 18: 373–377, 1998pmid:9692350
    OpenUrlPubMed
    1. Thomas DB,
    2. Franceschini N,
    3. Hogan SL,
    4. Ten Holder S,
    5. Jennette CE,
    6. Falk RJ,
    7. Jennette JC
    : Clinical and pathologic characteristics of focal segmental glomerulosclerosis pathologic variants. Kidney Int 69: 920–926, 2006pmid:16518352
    OpenUrlCrossRefPubMed
    1. Laradi A,
    2. Mallet A,
    3. Beaufils H,
    4. Allouache M,
    5. Martinez F
    : HIV-associated nephropathy: Outcome and prognosis factors. Groupe d’ Etudes Néphrologiques d’Ile de France. J Am Soc Nephrol 9: 2327–2335, 1998pmid:9848787
    OpenUrlAbstract
  35. ↵
    1. Williams DI,
    2. Williams DJ,
    3. Williams IG,
    4. Unwin RJ,
    5. Griffiths MH,
    6. Miller RF
    : Presentation, pathology, and outcome of HIV associated renal disease in a specialist centre for HIV/AIDS. Sex Transm Infect 74: 179–184, 1998pmid:9849552
    OpenUrlAbstract
  36. ↵
    1. Freedman BI,
    2. Soucie JM,
    3. Stone SM,
    4. Pegram S
    : Familial clustering of end-stage renal disease in blacks with HIV-associated nephropathy. Am J Kidney Dis 34: 254–258, 1999pmid:10430971
    OpenUrlPubMed
  37. ↵
    1. Kopp JB,
    2. Smith MW,
    3. Nelson GW,
    4. Johnson RC,
    5. Freedman BI,
    6. Bowden DW,
    7. Oleksyk T,
    8. McKenzie LM,
    9. Kajiyama H,
    10. Ahuja TS,
    11. Berns JS,
    12. Briggs W,
    13. Cho ME,
    14. Dart RA,
    15. Kimmel PL,
    16. Korbet SM,
    17. Michel DM,
    18. Mokrzycki MH,
    19. Schelling JR,
    20. Simon E,
    21. Trachtman H,
    22. Vlahov D,
    23. Winkler CA
    : MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis. Nat Genet 40: 1175–1184, 2008pmid:18794856
    OpenUrlCrossRefPubMed
  38. ↵
    1. Genovese G,
    2. Tonna SJ,
    3. Knob AU,
    4. Appel GB,
    5. Katz A,
    6. Bernhardy AJ,
    7. Needham AW,
    8. Lazarus R,
    9. Pollak MR
    : A risk allele for focal segmental glomerulosclerosis in African Americans is located within a region containing APOL1 and MYH9. Kidney Int 78: 698–704, 2010pmid:20668430
    OpenUrlCrossRefPubMed
  39. ↵
    1. Fessel WJ
    : Systemic lupus erythematosus in the community. Incidence, prevalence, outcome, and first symptoms; the high prevalence in black women. Arch Intern Med 134: 1027–1035, 1974pmid:4433183
    OpenUrlCrossRefPubMed
PreviousNext
Back to top

In this issue

Clinical Journal of the American Society of Nephrology: 7 (6)
Clinical Journal of the American Society of Nephrology
Vol. 7, Issue 6
June 07, 2012
  • Table of Contents
  • Table of Contents (PDF)
  • Index by author
View Selected Citations (0)
Print
Download PDF
Sign up for Alerts
Email Article
Thank you for your help in sharing the high-quality science in CJASN.
Enter multiple addresses on separate lines or separate them with commas.
Collapsing Glomerulopathy in 19 Patients with Systemic Lupus Erythematosus or Lupus-Like Disease
(Your Name) has sent you a message from American Society of Nephrology
(Your Name) thought you would like to see the American Society of Nephrology web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Collapsing Glomerulopathy in 19 Patients with Systemic Lupus Erythematosus or Lupus-Like Disease
Steven P. Salvatore, Laura M. C. Barisoni, Andrew M. Herzenberg, Praveen N. Chander, Volker Nickeleit, Surya V. Seshan
CJASN Jun 2012, 7 (6) 914-925; DOI: 10.2215/CJN.11751111

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Collapsing Glomerulopathy in 19 Patients with Systemic Lupus Erythematosus or Lupus-Like Disease
Steven P. Salvatore, Laura M. C. Barisoni, Andrew M. Herzenberg, Praveen N. Chander, Volker Nickeleit, Surya V. Seshan
CJASN Jun 2012, 7 (6) 914-925; DOI: 10.2215/CJN.11751111
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like

Jump to section

  • Article
    • Summary
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Disclosures
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data Supps
  • Info & Metrics
  • View PDF

More in this TOC Section

Original Articles

  • Association of Polypharmacy with Kidney Disease Progression in Adults with CKD
  • The Effect of Atrasentan on Kidney and Heart Failure Outcomes by Baseline Albuminuria and Kidney Function
  • Collectin11 and Complement Activation in IgA Nephropathy
Show more Original Articles

Clinical Immunology and Pathology

  • Clinical and Histopathologic Characteristics Associated with Renal Outcomes in Lupus Nephritis
  • Staphylococcus Infection–Associated GN – Spectrum of IgA Staining and Prevalence of ANCA in a Single-Center Cohort
  • Glomerular Pathology in Dent Disease and Its Association with Kidney Function
Show more Clinical Immunology and Pathology

Cited By...

  • APOL1 Gene -- Implications for Systemic Lupus Erythematosus
  • Haemophagocytic lymphohistiocytosis with collapsing lupus podocytopathy as an unusual manifestation of systemic lupus erythematosus with APOL1 double-risk alleles
  • Collapsing glomerulopathy, the Saudi Arabian scenario: A study of 31 cases and a review of literature
  • Collapsing glomerulopathy in systemic lupus erythematosus
  • Clinical-Morphological Features and Outcomes of Lupus Podocytopathy
  • The Revisited Classification of GN in SLE at 10 Years: Time to Re-Evaluate Histopathologic Lesions
  • Apolipoprotein L1 Risk Variants Associate with Systemic Lupus Erythematosus-Associated Collapsing Glomerulopathy
  • Collapsing Glomerulopathy in Systemic Lupus Erythematosus: An Extreme Form of Lupus Podocytopathy?
  • Google Scholar

Similar Articles

Related Articles

  • Collapsing Glomerulopathy in Systemic Lupus Erythematosus: An Extreme Form of Lupus Podocytopathy?
  • PubMed
  • Google Scholar

Articles

  • Current Issue
  • Early Access
  • Subject Collections
  • Article Archive
  • ASN Meeting Abstracts

Information for Authors

  • Submit a Manuscript
  • Trainee of the Year
  • Author Resources
  • ASN Journal Policies
  • Reuse/Reprint Policy

About

  • CJASN
  • ASN
  • ASN Journals
  • ASN Kidney News

Journal Information

  • About CJASN
  • CJASN Email Alerts
  • CJASN Key Impact Information
  • CJASN Podcasts
  • CJASN RSS Feeds
  • Editorial Board

More Information

  • Advertise
  • ASN Podcasts
  • ASN Publications
  • Become an ASN Member
  • Feedback
  • Follow on Twitter
  • Password/Email Address Changes
  • Subscribe to ASN Journals

© 2022 American Society of Nephrology

Print ISSN - 1555-9041 Online ISSN - 1555-905X

Powered by HighWire