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

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 case of lupus podocytopathy and a review of the literature

Portuguese Journal of Nephrology & Hypertension ◽

10.32932/pjnh.2021.04.116 ◽

2021 ◽

Vol 35 (1) ◽

pp. 39-42

Author(s):

José Silvano ◽

◽

Augusta Praça ◽

Inês Ferreira ◽

Ana Nunes ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Lupus Nephritis ◽

Lupus Erythematosus ◽

Minimal Change Disease ◽

Kidney Injury ◽

Mesangial Proliferation ◽

Foot Process ◽

Complex Deposition ◽

Lupus Podocytopathy

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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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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Approach to the Patient with Glomerular Disease

10.2310/tywc.12019 ◽

2018 ◽

Author(s):

Richard J. Glassock ◽

An S De Vriese ◽

Fernando C. Fervenza

Keyword(s):

Nephrotic Syndrome ◽

Renal Biopsy ◽

Rapidly Progressive Glomerulonephritis ◽

Chronic Glomerulonephritis ◽

Glomerular Diseases ◽

Diagnosis And Prognosis ◽

Protein Excretion ◽

Clinical Syndromes ◽

Organ Systems ◽

Therapeutic Decision Making

Glomerular diseases of the kidneys are associated with a limited array of clinical syndromes, including asymptomatic hematuria and/or proteinuria, acute nephritis, nephrotic syndrome, rapidly progressive glomerulonephritis, and chronic glomerulonephritis. The specific diseases that underlie these syndromes are numerous and heterogeneous. Broadly, they may be divided into primary and secondary disorders depending on whether the kidneys are the sole organs affected or whether other organ systems are also involved in the disease processes. A systematic approach involving a careful history, physical examination, assessment of renal function, and urinalysis (composition and microscopy) and protein excretion, combined with biochemical and serologic testing, can provide important clues to diagnosis and prognosis. Renal biopsy is often required for a complete and accurate diagnosis as well as a prognosis and therapeutic decision making. This review contains 4 figures, 6 tables and 92 references Key words: glomerular filtration rate, glomerulonephritis, hematuria, nephrotic syndrome, proteinuria, renal biopsy, serum complement

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Establishment of a novel nomogram for the clinically diagnostic prediction of minimal change disease, −a common cause of nephrotic syndrome

BMC Nephrology ◽

10.1186/s12882-020-02058-3 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Gaofei Yan ◽

Guanzhi Liu ◽

Xuefei Tian ◽

Lifang Tian ◽

Hao Wang ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Renal Biopsy ◽

Minimal Change Disease ◽

Clinical Manifestations ◽

Minimal Change ◽

Adult Patients ◽

Lasso Regression ◽

Glomerular Diseases ◽

Laboratory Test Results ◽

Primary Glomerular Diseases

Abstract Background Minimal change disease (MCD) is one of the major causes of nephrotic syndrome (NS). A confirmed MCD diagnosis mainly depends on renal biopsy at present, which is an invasive procedure with many potential risks. The overall incidence of complications caused by renal biopsy procedures has been reported as approximately 11 and 6.6% outside and within China, respectively. Unfortunately, there is currently no noninvasive procedure or practical classification method for distinguishing MCD from other primary glomerular diseases available. Method A total of 1009 adult patients who underwent renal biopsy between January 2017 and November 2019 were enrolled in this study. Twenty-five parameters extracted from patient demographics, clinical manifestations, and laboratory test results were statistically analysed. LASSO regression analysis was further performed on these parameters. The parameters with the highest area under the curve (AUC) were selected and used to establish a logistic diagnostic prediction model. Results Of the 25 parameters, 14 parameters were significantly different (P < 0.05). MCD patients were mostly younger (36 (22, 55) vs. 41 (28.75, 53)) and male (59% vs. 52%) and had lower levels of diastolic blood pressure (DBP) (79 (71, 85.5) vs. 80 (74, 89)) and IgG (5.42 (3.17, 6.36) vs. 9.38 (6.79, 12.02)) and higher levels of IgM (1.44 (0.96, 1.88) vs. 1.03 (0.71, 1.45)) and IgE (160 (46.7, 982) vs. 47.3 (19, 126)) than those in the non-MCD group. Using the LASSO model, we established a classifier for adults based on four parameters: DBP and the serum levels of IgG, IgM, IgE. We were able to clinically classify adult patients with NS into MCD and non-MCD using this model. The validation accuracy of the logistic regression model was 0.88. A nomogram based on these four classifiers was developed for clinical use that could predict the probability of MCD in adult patients with NS. Conclusions A LASSO model can be used to distinguish MCD from other primary glomerular diseases in adult patients with NS. Combining the model and the nomogram potentially provides a novel and valuable approach for nephrologists to diagnose MCD, avoiding the complications caused by renal biopsy.

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Horseshoe kidney with PLA2R-positive membranous nephropathy

BMC Nephrology ◽

10.1186/s12882-021-02488-7 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Shuai-Shuai Shi ◽

Xian-Zu Yang ◽

Xiao-Ye Zhang ◽

Hui-Dan Guo ◽

Wen-Feng Wang ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Renal Biopsy ◽

Membranous Nephropathy ◽

Horseshoe Kidney ◽

Glomerular Disease ◽

Urinary Stones ◽

Abdominal Ultrasonography ◽

Glomerular Diseases ◽

Structural Abnormalities ◽

Diagnosis Rate

Abstract Background Horseshoe kidney (HSK) is a common congenital defect of the urinary system. The most common complications are urinary tract infection, urinary stones, and hydronephrosis. HSK can be combined with glomerular diseases, but the diagnosis rate of renal biopsy is low due to structural abnormalities. There are only a few reports on HSK with glomerular disease. Here, we have reported a case of PLA2R-positive membranous nephropathy occurring in a patient with HSK. Case presentation After admission to the hospital due to oedema of both the lower extremities, the patient was diagnosed with nephrotic syndrome due to abnormal 24-h urine protein (7540 mg) and blood albumin (25 g/L) levels. Abdominal ultrasonography revealed HSK. The patient’s brother had a history of end-stage renal disease due to nephrotic syndrome. Therefore, the patient was diagnosed with PLA2R-positive stage II membranous nephropathy through renal biopsy under abdominal ultrasonography guidance. He was administered adequate prednisone and cyclophosphamide, and after 6 months of treatment, urinary protein excretion levels significantly decreased. Conclusion The risk and difficulty of renal biopsy in patients with HSK are increased due to structural abnormalities; however, renal biopsy can be accomplished through precise positioning with abdominal ultrasonography. In the literature, 20 cases of HSK with glomerular disease have been reported thus far. Because of the small number of cases, estimating the incidence rate of glomerular diseases in HSK is impossible, and the correlation between HSK and renal pathology cannot be stated. Further studies should be conducted and cases should be accumulated to elucidate this phenomenon.

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Difficult Renal Pathological Classification in a Case of Pediatric Nephrotic Syndrome

Case Reports in Nephrology and Dialysis ◽

10.1159/000484475 ◽

2017 ◽

Vol 7 (3) ◽

pp. 161-166

Author(s):

Hiroshi Yamaguchi ◽

Atsutoshi Shiratori ◽

Taku Nakagawa ◽

Kyoko Kanda ◽

Shigeo Hara ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Complete Remission ◽

Renal Biopsy ◽

Clinical Course ◽

Minimal Change ◽

Albumin Infusion ◽

Dense Deposits ◽

Old Japanese ◽

Foot Process ◽

The Impact

The underlying histopathology is very important in determining patient management, as the histopathology usually has direct repercussions on the treatment response and clinical course. However, the impact of the method used to assess renal biopsies, i.e., light microscopy (LM), immunofluorescence (IF), and electron microscopy (EM), on the occurrence of a difficult biopsy classification in the native kidneys of pediatric nephrotic patients is unknown. A 12-month-old Japanese boy was diagnosed with nephrotic syndrome (NS); he was administered prednisolone (60 mg/m2/day), and a continuous albumin infusion was started. A renal biopsy using LM revealed minimal change. However, an IF study showed granular staining for immunoglobulin G along the glomerular basement membrane. Therefore, he was diagnosed with membranous nephropathy (MN). As his proteinuria was so severe, we started immunosuppressant therapy and continued the albumin infusion for more than 2 months. However, he did not attain complete remission. A month later, EM examination of his renal biopsy showed extensive foot process fusion without electron-dense deposits. Although the result of the IF study suggested MN, the results of the LM and EM studies indicated minimal change. We finally diagnosed the patient with minimal change NS, in consideration of his clinical condition and course. Because of the failure of previous treatments, pulse steroid therapy was started. After five rounds of therapy the patient attained complete remission. A difficult renal biopsy finding classification, dependent on the diagnostic method used, might occur in the native kidneys of pediatric nephrotic patients. Therefore, a diagnosis should be made after considering all renal biopsy findings and the clinical course.

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Approach to the Patient with Glomerular Disease

10.2310/nephro.12019 ◽

2018 ◽

Author(s):

Richard J. Glassock ◽

An S De Vriese ◽

Fernando C. Fervenza

Keyword(s):

Nephrotic Syndrome ◽

Renal Biopsy ◽

Rapidly Progressive Glomerulonephritis ◽

Chronic Glomerulonephritis ◽

Glomerular Diseases ◽

Diagnosis And Prognosis ◽

Protein Excretion ◽

Clinical Syndromes ◽

Organ Systems ◽

Therapeutic Decision Making

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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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Lupus-like membranous nephropathy. Is it lupus? Report of 5 cases in a reference hospital in Mexico

Lupus ◽

10.1177/09612033211013584 ◽

2021 ◽

pp. 096120332110135

Author(s):

Luis Manuel Ramírez-Gómez ◽

Ivette Ruiz-Leija ◽

David Martínez-Galla ◽

Jaime Antonio Borjas-García ◽

Carlos Abud-Mendoza ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Lupus Nephritis ◽

Renal Biopsy ◽

Mycophenolic Acid ◽

Lupus Erythematosus ◽

Antinuclear Antibodies ◽

Classification Criteria ◽

Normal Limits ◽

Extrarenal Manifestations

Introduction: Lupus nephritis requires antinuclear antibodies as classification criteria. There is a group of patients with nephrotic syndrome and conclusive histopathological findings for lupus nephritis, without classification criteria for systemic lupus erythematosus (SLE) or extrarenal manifestations. These groups of patients have been described as “lupus-like” nephritis or “renal-limited lupus nephritis”. Methods: Renal biopsy with histopathological evaluation with “full-house” immune-reactants in patients with negative antinuclear antibodies. Results: We report four cases with nephrotic syndrome and one with hematuria-proteinuria syndrome: two with impaired glomerular filtration rate and three with preserved renal function; urinary sediment with hematuria without dysmorphia and without extrarenal manifestations for autoimmune disease, negative antinuclear antibodies (ANA) and anti-double stranded DNA (anti-dsDNA); normal C3 and C4 complement levels. Renal biopsy in all cases was consistent for lupus nephritis class V. All patients received treatment as lupus nephritis protocol; only one case received induction with cyclophosphamide and methylprednisolone boluses, the rest received mycophenolic acid and prednisone as induction and maintenance. Two of the cases induced with mycophenolic acid relapsed, requiring cyclophosphamide for 6 months, achieving complete remission. All patients received renin-angiotensin-aldosterone system blockade and hydroxychloroquine. At follow-up, 4 cases still have negative antibodies and are without extrarenal manifestations for SLE classification criteria. The other case, during pregnancy several years after initial diagnosis, had preeclampsia with nephrotic proteinuria and a new determination of positive ANA and anti-dsDNA antibodies, complement levels below normal limits. Conclusion: The follow-up of patients with membranous glomerulopathy must be close; lupus like nephritis may be the first manifestation of the disease.

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Antinuclear Antibody-Negative Lupus Nephritis with Full House Nephropathy: A Case Report and Review of the Literature

American Journal of Nephrology ◽

10.1159/000443747 ◽

2015 ◽

Vol 42 (6) ◽

pp. 451-459 ◽

Cited By ~ 22

Author(s):

Sierra C. Simmons ◽

Maxwell L. Smith ◽

April Chang-Miller ◽

Mira T. Keddis

Keyword(s):

Lupus Nephritis ◽

Renal Biopsy ◽

Lupus Erythematosus ◽

Antinuclear Antibody ◽

Leukocytoclastic Vasculitis ◽

Kidney Injury ◽

Mixed Cryoglobulinemia ◽

Close Monitoring ◽

Glomerular Diseases

Lupus nephritis (LN) is a serious and common complication of systemic lupus erythematosus (SLE) that predisposes to significant morbidity and mortality. Studies show that prompt diagnosis and treatment improves patient survival. We present a case of a 49-year-old female with an atypical presentation of LN who initially presented with new-onset hypertension, edema, arthritis, serositis and recently diagnosed leukocytoclastic vasculitis who later developed acute kidney injury, hematuria and nephrotic syndrome. Laboratory testing showed mixed cryoglobulinemia and elevated perinuclear anti-neutrophil cytoplasmic (p-ANCA) and myeloperoxidase (MPO) antibodies. SLE-related serologies were negative. Kidney biopsy showed diffuse proliferative global glomerulonephritis with a full-house nephropathy pattern on immunofluorescence suggestive of LN. Due to high clinical suspicion and renal biopsy findings, she was treated for LN with prompt renal response to immunosuppression. Cryoglobulins, p-ANCA and MPO titers normalized and the negative SLE serologies remained negative. Literature review on antinuclear antibody (ANA)-negative and seronegative LN revealed the following patient presentations: (1) renal-limited or renal and extra-renal manifestations of SLE with negative serologies and (2) renal and extra-renal manifestations of SLE with negative serologies at presentation who develop positive serologies later in follow-up. Both groups represent a unique and challenging cohort of patients who may require longer follow-up and further testing to rule out other glomerular diseases that may mimic LN on renal biopsy. The absence of SLE-related serologies should be weighed against a high pre-test probability of ANA-negative or seronegative LN. If highly suspected, the patient should be treated promptly with close monitoring.

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