A case of lupus podocytopathy and a review of the literature

Nephrotic syndrome in systemic lupus erythematosus patients with histological evidence of minimal change disease, mesangial proliferation or focal and segmental glomerulosclerosis on light microscopy, represents a distinct clinical entity – lupus podocytopathy. This entity is characterized by a diffuse foot process effacement on electron microscopy and by absence of subepithelial or subendothelial immune -complex deposition. We report the case of a 49 -year -old woman admitted on suspicion of lupus nephritis flare, characterized by nephrotic syndrome and acute kidney injury, whose renal biopsy revealed histological features of lupus podocytopathy. Six months after discharge, under prednisolone and azathioprine, she presented 300 mg/day proteinuria, normal kidney function, without hematuria. A review of the pathogenesis, clinical features, diagnostic criteria, treatment and prognosis of lupus podocytopathy is provided. This case highlights the mounting evidence that lupus podocytopathy encompasses distinct clinical and morphological features, that should be included in the upcoming pathological classification of lupus nephritis.

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Recurrent podocytopathy in a patient with systemic lupus erythematosus

SAGE Open Medical Case Reports ◽

10.1177/2050313x17695997 ◽

2017 ◽

Vol 5 ◽

pp. 2050313X1769599

Author(s):

Shereen Paramalingam ◽

Daniel D Wong ◽

Gursharan K Dogra ◽

Johannes C Nossent

Keyword(s):

Electron Microscopy ◽

Systemic Lupus Erythematosus ◽

Nephrotic Syndrome ◽

Lupus Erythematosus ◽

Systemic Lupus ◽

Systemic Lupus Erythematosus Activity ◽

Growing Body ◽

Foot Process ◽

Lupus Podocytopathy

Podocytopathy in systemic lupus erythematosus is characterised by diffuse foot process effacement without significant peripheral capillary wall immune deposits as seen on electron microscopy. Lupus podocytopathy falls outside the scope of the current International Society of Nephrology and the Renal Pathology Society classification of lupus nephritis. We present a case of relapsing podocytopathy with nephrotic syndrome occurring simultaneously with two extra-renal and serological disease flares, which makes it likely that podocytopathy was related to systemic lupus erythematosus activity. This case adds to the growing body of evidence that lupus podocytopathy must be considered in the differential diagnosis of systemic lupus erythematosus patients presenting with nephrotic syndrome.

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Delayed Onset Minimal Change Disease as a Manifestation of Lupus Podocytopathy

Clinics and Practice ◽

10.3390/clinpract11040089 ◽

2021 ◽

Vol 11 (4) ◽

pp. 747-754

Author(s):

Rasha Aly ◽

Xu Zeng ◽

Ratna Acharya ◽

Kiran Upadhyay

Keyword(s):

Renal Function ◽

Lupus Erythematosus ◽

Minimal Change Disease ◽

Normal Serum ◽

Minimal Change ◽

Renal Histology ◽

Foot Process ◽

Lupus Podocytopathy

Lupus podocytopathy (LP) is an uncommon manifestation of systemic lupus erythematosus (SLE) and is not included in the classification of lupus nephritis. The diagnosis of LP is confirmed by the presence of diffuse foot process effacement in the absence of capillary wall deposits with or without mesangial immune deposits in a patient with SLE. Here we describe a 13-year-old female who presented with nephrotic syndrome (NS) seven years after the diagnosis of SLE. The renal function had been stable for seven years since the SLE diagnosis, as manifested by the normal serum creatinine, serum albumin and absence of proteinuria. Renal biopsy showed evidence of minimal change disease without immune complex deposits or features of membranous nephropathy. Renal function was normal. The patient had an excellent response to steroid therapy with remission within two weeks. The patient remained in remission five months later during the most recent follow-up. This report highlights the importance of renal histology to determine the accurate etiology of NS in patients with SLE. Circulating factors, including cytokines such as interleukin 13, may play a role in the pathophysiology of LP and needs to be studied further in future larger studies.

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Is podocytopathy another image of renal affection in p-SLE?

Pediatric Rheumatology ◽

10.1186/s12969-021-00547-9 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Hend H. Abdelnabi

Keyword(s):

Lupus Erythematosus ◽

Renal Involvement ◽

Histopathological Analysis ◽

Immune Deposits ◽

Foot Process ◽

Lupus Podocytopathy ◽

Focal Segmental Sclerosis ◽

Nephrotic Range Proteinuria

Abstract Background Lupus podocytopathy (LP) is a renal affection described in systemic lupus erythematosus (SLE) patients with nephrotic range proteinuria, characterized by diffuse foot process effacement without immune deposits and glomerular proliferation. This study describes LP, its pathological features and outcomes of pediatric (p-SLE) patients in comparison to the usual lupus nephritis (LN) cases. Methodology A retrospective cohort study conducted on a 10-year registration (2010–2019) of 140 p-SLE patients at the Pediatric Department, Tanta University. Histopathological analysis with light microscopy (LM) and immunofluorescence (IF) of all renal biopsies were evaluated according to the International Society of Nephrology Renal Pathology Society (ISN/RPS) grading system. In addition, some biopsies were examined with electron microscopy (EM). Results Eighty-six p-SLE cases (61.4%) had renal involvement; seventy-nine biopsies (91.86%) of them met the classification criteria of LN as defined by ISN/RPS system. Five biopsies were normal (MCD) and two showed focal segmental sclerosis (FSGN) that did not meet any known classification of LN. Hence, they were reevaluated using EM that revealed diffuse effaced podocytes without glomerular sub-epithelial, endocapillary or basement membrane immune deposits, and were classified as having lupus podocytopathy, representing (8.14%) of all LN biopsies. Those seven cases showed good response to steroids with a complete remission duration of 3.40 ± 1.95 weeks. However, some case had 1–3 relapses during the duration of follow up. Conclusions LP is a spectrum of p-SLE, not an association as it is related to disease activity and its initial presentation.

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Identification of Lupus Podocytopathy with Coexistent Glomerular Diseases – A Case Report

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqaa161.149 ◽

2020 ◽

Vol 154 (Supplement_1) ◽

pp. S68-S69

Author(s):

L Ding ◽

J Tomaszewski ◽

L Liu ◽

B Murray

Keyword(s):

Nephrotic Syndrome ◽

Diabetic Nephropathy ◽

Lupus Nephritis ◽

Renal Biopsy ◽

Glomerular Diseases ◽

Nephrotic Proteinuria ◽

Immune Deposits ◽

Foot Process ◽

Lupus Podocytopathy ◽

Dose Prednisone

Abstract Introduction/Objective Lupus podocytopathy (LP), featured by nephrotic syndrome, is a unique subtype of lupus nephritis that mimics minimal change disease or primary focal segmental glomerulosclerosis (FSGS) on renal biopsy with diffuse podocyte foot process effacement and no capillary-loop immune deposits. LP usually presents on a background of ISN/RPS class I or class II lupus nephritis, and very rarely may present without immune deposits. Diagnosis of LP, when confounded by other glomerular diseases associated with nephrotic syndrome, can be very challenging and requires thorough clinical and pathology correlations. Methods Here we report a case of LP in a patient with nephrotic syndrome and multiple comorbidities affecting kidneys. A 24-year-old female with type-I diabetes, psoriasis, and intermittent arthritis/rash of unknown etiology, presented with abrupt onset of nephrotic proteinuria attributed to recent low dose prednisone therapy, and renal insufficiency. A renal biopsy showed nodular glomerulosclerosis and FSGS. No immune deposits were identified by immunofluorescence or electron microscopy. Ultrastructurally there was also diffuse glomerular basement membrane thickening and over 90% podocyte foot process effacement. With no established systemic lupus erythematosus (SLE), the case was initially diagnosed as diabetic nephropathy with coexistent FSGS as the etiologies for nephrotic proteinuria, and the patient was put on ACEI and diuretics. However, massive proteinuria persisted, and the patient also developed pancytopenia. Serology concurrent with the biopsy came out later showing positive autoantibodies against dsDNA, Smith, and Histone. With continued worsening of creatinine, a renal biopsy was repeated revealing essentially similar findings to the first biopsy. Results Integrating the serology results and clinical presentation, SLE was favored. The pathology findings were re- evaluated and considered to be most consistent with LP and coexistent diabetic nephropathy, with FSGS either a component of LP or an independent lesion secondary to diabetes or hypertension. The patient was started with high dose prednisone at 60 mg/day. One month later, her proteinuria, serum creatinine, pancytopenia, skin rash, and arthritis were all significantly improved. Conclusion LP can be easily masked by coexistent glomerular diseases. Sufficient awareness of the entity is necessary for the appropriate diagnosis and treatment.

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A patient with systemic lupus erythematosus and lupus nephritis: A 12-year follow-up

Vojnosanitetski pregled ◽

10.2298/vsp1108705j ◽

2011 ◽

Vol 68 (8) ◽

pp. 705-708

Author(s):

Natasa Jovanovic ◽

Jasmina Markovic-Lipkovski ◽

Stevan Pavlovic ◽

Biljana Stojimirovic

Keyword(s):

Systemic Lupus Erythematosus ◽

Nephrotic Syndrome ◽

Mycophenolate Mofetil ◽

Lupus Nephritis ◽

Lupus Erythematosus ◽

Kidney Biopsy ◽

Immunosuppressive Drugs ◽

Systemic Lupus ◽

Younger Women ◽

The Right

Introduction. Systemic lupus erythematosus (SLE) is a chronic immunological disease causing a significant morbidity and mortality in younger women and involving several organs and systems, most often the kidneys, being consequently the incidence of lupus nephritis (LN) about 60%. Case report. We reported a 57 year-old patient with the diagnosed SLE in 1995. Pathohistological analysis of kidney biopsy revealed LN type V. The patient was treated with corticosteroid pulses and azathioprine during one year. A remission was achieved and maintained with prednisone, 15 mg daily. Nephrotic relapse was diagnosed in 2006 and the second kidney biopsy revealed recent kidney infarction due to extensive vasculitis. Soon, a cerebrovascul insult developed and CT-scan revealed endocranial infarctus. The patient was treated with corticosteroids and cyclophosphamide pulses (totally VI monthly pulses), and also with low-molecular heparine, anticoagulants and salicylates because of the right leg phlebothrombosis. After the pulses, the patient was adviced to take prednisone 20 mg daily and azothioprine 100 mg daily, and 6 months later mycophenolate mofetil because of persistent active serological immunological findings (ANA 1 : 320) and nephrotic syndrome. Mycophenolate mofetil was efficient in inducing and maintaining remission of nephrotic syndrome. Conclusion. The aim of LN treatment is to achieve and maintain remission, improve patients? outcome, reduce the toxicity of immunosuppressive drugs and the incidence of relapses. Mycophenolate mofetil was shown to be efficient in inducing and maintaining remission of nephrotic syndrome in the frame of LN.

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Mesangial lupus nephritis with associated nephrotic syndrome.

Journal of the American Society of Nephrology ◽

10.1681/asn.v871199 ◽

1997 ◽

Vol 8 (7) ◽

pp. 1199-1204

Author(s):

N Stankeviciute ◽

W Jao ◽

A Bakir ◽

J P Lash

Keyword(s):

Nephrotic Syndrome ◽

Lupus Nephritis ◽

Lupus Erythematosus ◽

World Health ◽

Clinical Tool ◽

Laboratory Findings ◽

Glomerular Lesion ◽

Health Organization ◽

Lupus Glomerulonephritis ◽

Nephrotic Range Proteinuria

Patients with mesangial proliferative lupus glomerulonephritis (World Health Organization class II) are generally believed to have only mild to moderate proteinuria and normal renal function. However, there have been several reports of patients with mesangial lupus with nephrotic-range proteinuria. In this report, we present two additional cases and review the literature. Of seven reported cases, persistent nephrotic syndrome was observed in four, morphologic transformation occurred in three, and all but one presented with varying degrees of azotemia. These cases reinforce the concept that in systemic lupus erythematosus, laboratory findings may not correlate well with the underlying glomerular lesion, and therefore, the renal biopsy is an essential clinical tool in the approach to lupus nephritis.

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Minimal Change Disease as a Secondary and Reversible Event of a Renal Transplant Case with Systemic Lupus Erythematosus

Case Reports in Nephrology ◽

10.1155/2015/987212 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Elena Gkrouzman ◽

Kyriakos A. Kirou ◽

Surya V. Seshan ◽

James M. Chevalier

Keyword(s):

Systemic Lupus Erythematosus ◽

Nephrotic Syndrome ◽

Renal Transplant ◽

Transplant Recipient ◽

Lupus Erythematosus ◽

Minimal Change Disease ◽

Iliac Vein ◽

Minimal Change ◽

Systemic Lupus ◽

Vein Stenosis

Secondary causes of minimal change disease (MCD) account for a minority of cases compared to its primary or idiopathic form and provide ground for consideration of common mechanisms of pathogenesis. In this paper we report a case of a 27-year-old Latina woman, a renal transplant recipient with systemic lupus erythematosus (SLE), who developed nephrotic range proteinuria 6 months after transplantation. The patient had recurrent acute renal failure and multiple biopsies were consistent with MCD. However, she lacked any other features of the typical nephrotic syndrome. An angiogram revealed a right external iliac vein stenosis in the region of renal vein anastomosis, which when restored resulted in normalization of creatinine and relief from proteinuria. We report a rare case of MCD developing secondary to iliac vein stenosis in a renal transplant recipient with SLE. Additionally we suggest that, in the event of biopsy-proven MCD presenting as an atypical nephrotic syndrome, alternative or secondary, potentially reversible, causes should be considered and explored.

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Clinical Characteristics and Outcomes of Adults with Nephrotic Syndrome Due to Minimal Change Disease

Journal of Clinical Medicine ◽

10.3390/jcm10163632 ◽

2021 ◽

Vol 10 (16) ◽

pp. 3632

Author(s):

Sophia Lionaki ◽

Evangelos Mantios ◽

Ioanna Tsoumbou ◽

Smaragdi Marinaki ◽

George Makris ◽

...

Keyword(s):

Acute Kidney Injury ◽

Nephrotic Syndrome ◽

Minimal Change Disease ◽

Kidney Injury ◽

Spontaneous Remission ◽

Minimal Change ◽

Adult Onset ◽

Potential Risk Factors ◽

The Mean ◽

End Stage

Purpose: Minimal change disease (MCD) is considered a relatively benign glomerulopathy, as it rarely progresses to end-stage kidney disease. The aim of this study was to describe the characteristics and outcomes of adults with MCD and identify potential risk factors for relapse. Patients & Methods: We retrospectively studied a cohort of adults with biopsy-proven MCD in terms of clinical features and treatment outcomes. Baseline characteristics and outcomes were recorded and predictors of relapse were analyzed using logistic regression multivariate analysis. Results: 59 patients with adult-onset primary MCD with nephrotic syndrome were included. Mean serum creatinine at diagnosis was 0.8 mg/dL (±2.5) and estimated GFR (eGFR) was 87 mL/min/1.73 m2 (±29.5). Mean serum albumin was 2.5 g/dL (±0.8) and 24 h proteinuria 6.8 g (±3.7). Microscopic hematuria was detected in 35 (58.5%) patients. 42 patients received prednisone alone, six patients received prednisone plus cyclophosphamide, five patients received prednisone plus cyclosporine, one patient received prednisone plus rituximab and five patients did not receive immunosuppression at all since they achieved spontaneous remission. During a mean follow up time of 34.7(22.1) months, 46.1% of patients experienced at least one episode of relapse. The mean age of patients who did not experience a relapse was significantly higher than that of patients who relapsed while relapsers had a significantly longer duration of 24 h proteinuria prior to biopsy compared to non-relapsers. Overall, 10% of patients experienced acute kidney injury while the mean eGFR at the end was 82 mL/min/1.73 m2 (±29.1) and one patient ended up in chronic dialysis. Overall, the proportion of non-relapsers, who experienced acute kidney injury (17%) was significantly higher than the one recorded among relapsers (0%).Conclusion: In this series of patients, almost 46% of adult-onset nephrotic MCD patients experienced a relapse, although their renal progression was rare. Younger onset age was an independent risk factor for relapse in adult-onset MCD patients.

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Urine Biomarkers to Predict Response to Lupus Nephritis Therapy in Children and Young Adults

The Journal of Rheumatology ◽

10.3899/jrheum.161128 ◽

2017 ◽

Vol 44 (8) ◽

pp. 1239-1248 ◽

Cited By ~ 17

Author(s):

Hermine I. Brunner ◽

Michael R. Bennett ◽

Gaurav Gulati ◽

Khalid Abulaban ◽

Marisa S. Klein-Gitelman ◽

...

Keyword(s):

Lupus Nephritis ◽

Lupus Erythematosus ◽

Transforming Growth Factor ◽

Kidney Biopsy ◽

Characteristic Curve ◽

Kidney Injury ◽

Transforming Growth Factor Β ◽

Response To Therapy ◽

Spot Urine ◽

Urine Biomarkers

Objective.To delineate urine biomarkers that forecast response to therapy of lupus nephritis (LN).Methods.Starting from the time of kidney biopsy, patients with childhood-onset systemic lupus erythematosus who were diagnosed with LN were studied serially. Levels of 15 biomarkers were measured in random spot urine samples, including adiponectin, α-1-acid glycoprotein (AGP), ceruloplasmin, hemopexin, hepcidin, kidney injury molecule 1, monocyte chemotactic protein-1, lipocalin-like prostaglandin D synthase (LPGDS), transforming growth factor-β (TGF-β), transferrin, and vitamin D binding protein (VDBP).Results.Among 87 patients (mean age 15.6 yrs) with LN, there were 37 treatment responders and 50 nonresponders based on the American College of Rheumatology criteria. At the time of kidney biopsy, levels of TGF-β (p < 0.0001) and ceruloplasmin (p = 0.006) were significantly lower among responders than nonresponders; less pronounced differences were present for AGP, hepcidin, LPGDS, transferrin, and VDBP (all p < 0.05). By Month 3, responders experienced marked decreases of adiponectin, AGP, transferrin, and VDBP (all p < 0.01) and mean levels of these biomarkers were all outstanding (area under the receiver-operating characteristic curve ≥ 0.9) for discriminating responders from nonresponders. Patient demographics and extrarenal disease did not influence differences in biomarker levels between response groups.Conclusion.Low urine levels of TGF-β and ceruloplasmin at baseline and marked reduction of AGP, LPGDS, transferrin, or VDBP and combinations of other select biomarkers by Month 3 are outstanding predictors for achieving remission of LN. If confirmed, these results can be used to help personalize LN therapy.

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P0338CRUMBS HOMOLOG2-EZRIN SIGNALING INDUCED PODOCYTE INJURY, LEADING TO MINIMAL-CHANGE DISEASE(MCD) AND FOCAL SEGMENTAL GLOMERULOSCLEROSIS(FSGS)

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa144.p0338 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Ichiro Hada

Keyword(s):

Electron Microscopy ◽

Nephrotic Syndrome ◽

Cell Line ◽

Focal Segmental Glomerulosclerosis ◽

Minimal Change Disease ◽

Immunofluorescence Microscopy ◽

Minimal Change ◽

Podocyte Injury ◽

Heavy Proteinuria ◽

Foot Process

Abstract Background and Aims The etiology and cellular pathogenesis of podocyte injury leading to minimal-change disease (MCD) and focal segmental glomerulosclerosis (FSGS) remain largely obscure. Genetic mutation of crumbs homolog 2 (CRB2) is a cause of congenital nephrotic syndrome. Type-1 transmembrane proteins including CRB2 transduce outside-in signals that are involved in various cellular events including changes in the cytoskeletal network. The aim of the present study is to determine whether alteration of CRB2-mediated signaling in podocytes causes MCD and FSGS. Method Mice were immunized with a partial recombinant protein including the extracellular part of mouse CRB2. Urinalysis was obtained, and the kidney was subjected to histopathology. Kidney samples were also subjected to immunofluorescence microscopy and glomerular isolation to determine whether activation of the ezrin/radixin/moesin (ERM) family of cross-linkers between plasma membrane proteins and the actin cytoskeleton is involved in the pathogenesis of this nephrotic model. A CRB2-expressing mouse podocyte cell line was generated and incubated with anti-CRB2 antibody, and cell lysates were subjected to immunoblot analysis of ERM phosphorylation. The presence of anti-CRB2 antibody in the serum was determined by Western blot analysis. Results Apparent anti-CRB2 antibody was detected in the serum from 4 weeks onward. Immunized mice developed proteinuria at 4 weeks, which continued at least until 29 weeks. Mice developing extremely heavy proteinuria also developed hematuria from 18 weeks onward. Light microscopy revealed MCD in mice with proteinuria alone and FSGS in mice with heavy proteinuria and hematuria. Immunofluorescence microscopy revealed positive granular IgG staining in podocyte foot processes, but not complement C3. Electron microscopy and immuno-electron microscopy revealed alteration of actin organization associated with prominent foot process effacement. Strong phosphorylation of ezrin was observed in the glomerulus from the proteinuric stage and in the cellular lysates from the CRB2-expressing podocyte cell line incubated with anti-CRB2 antibody. Conclusion The current data revealed that binding of anti-CRB2 antibody to the extracellular domain of CRB2 on the podocyte foot process activated the ezrin-cytoskeleton network, leading to podocyte injury. Our data also indicated that signaling by this one molecular can induce two different phenotypes of glomerular injury: MCD and FSGS. In our model, the signaling was activated by anti-CRB2 antibody, but in patients with nephrotic syndrome the CRB2 ligands remain unknown. Therefore, it will be important to identify the soluble factors interacting with CRB2, which may be novel factors contributing to the pathogenesis of MCD and FSGS.

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