Discovery of Autoantibodies Targeting Nephrin in Minimal Change Disease Supports a Novel Autoimmune Etiology

2021 ◽  
pp. ASN.2021060794
Author(s):  
Andrew Watts ◽  
Keith Keller ◽  
Gabriel Lerner ◽  
Ivy Rosales ◽  
A. Collins ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Animal Studies ◽  
Minimal Change Disease ◽  
Molecular Classification ◽  
Minimal Change ◽  
Filtration Barrier ◽  
Steroid Dependent ◽  
Renal Biopsies ◽  
End Stage ◽  
Autoimmune Etiology

Background Failure of the glomerular filtration barrier, primarily by loss of slit diaphragm architecture, underlies nephrotic syndrome in minimal change disease. The etiology remains unknown. The efficacy of B cell-targeted therapies in some patients, together with the known proteinuric effect of antinephrin antibodies in rodent models, prompted us to hypothesize that nephrin autoantibodies may be present in patients with minimal change disease. Methods We evaluated sera from patients with minimal change disease enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) cohort and from our own institutions for circulating nephrin autoantibodies by indirect ELISA and by immunoprecipitation of full-length nephrin from human glomerular extract or a recombinant purified extracellular domain of human nephrin. We also evaluated renal biopsies from our institutions for podocyte-associated punctate IgG colocalizing with nephrin by immunofluorescence Results In two independent patient cohorts, we identified in a subset of patients with minimal change disease circulating nephrin autoantibodies during active disease that were significantly reduced or absent during treatment response. We correlated the presence of these autoantibodies with podocyte-associated punctate IgG in renal biopsies from our institutions. We also identified a patient with steroid-dependent childhood minimal change disease that progressed to end-stage kidney disease; she developed a massive posttransplant recurrence of proteinuria that was associated with high pretransplant circulating nephrin autoantibodies. Conclusions Our discovery of nephrin autoantibodies in a subset of adults and children with minimal change disease aligns with published animal studies and provides further support for an autoimmune etiology. We propose a new molecular classification of nephrin autoantibody minimal change disease to serve as framework for instigation of precision therapeutics for these patients.

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

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.

scholarly journals The Transition From Minimal Change Disease to Focal and Segmental Glomerulosclerosis in a Patient With Nephrotic Syndrome: a Case Report

2021 ◽  
Author(s):  
Long Tang ◽  
Zhen Cai ◽  
Yuan Meng ◽  
Wen-jing Zhao ◽  
Su-Xia Wang
Keyword(s):  
Nephrotic Syndrome ◽  
Minimal Change Disease ◽  
Kidney Biopsy ◽  
Elevated Serum ◽  
Minimal Change ◽  
Segmental Glomerulosclerosis ◽  
Stage Renal Disease ◽  
End Stage ◽  
The Relationship

Abstract Background:Although minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) have been described as two separate forms of nephrotic syndrome(NS), they are not completely independent. We report a patient presenting a transition from MCD to FSGS, review the literature and explore the relationship between the two diseases.Case presentation:A 42-year-old male welder, Asian, presenting lower extremity edema and elevated serum creatinine, had laboratory exams indicating NS and end-stage renal disease(ESRD). The patient had a kidney biopsy 20 years earlier for NS, which indicated MCD, and this repeated kidney biopsy suggested FSGS. After treatment follow-up, the patient was eventually admitted to renal replacement therapy. Conclusions:MCD and FSGS may be different stages of the same disease. The transition from MCD to FSGS in this case indicates the progression of the disease, which may be related to the excessive metal caused by occupation.

scholarly journals RENAL BIOPSY IN PAEDIATRIC POPULATION

1969 ◽  
Vol 3 (2) ◽  
pp. 314-317
Author(s):  
AHMAD ZEB KHAN ◽  
RIAZ GUL ◽  
AZIZ AHMAD
Keyword(s):  
Nephrotic Syndrome ◽  
Renal Biopsy ◽  
Focal Segmental Glomerulosclerosis ◽  
Minimal Change Disease ◽  
Paediatric Population ◽  
Minimal Change ◽  
Segmental Glomerulosclerosis ◽  
Renal Biopsies ◽  
A Prospective Study ◽  
Nephrotic Range Proteinuria

OBJECTIVE: To find out the pattern of glomerulopathies in paediatric population, undergoing renalbiopsy at Khyber Teaching Hospital, Peshawar.METHODS: This was a prospective study carried out at the department of Nephrology at Khyber TeachingHospital, Peshawar from June 2010 till June 2012. Ultrasound guided percutaneous renal biopsies werecarried out in patients with the finding of; 1 ) Nephrotic range proteinuria in children. 2) Non-Nephroticrange proteinuria with evidence of hypertension / haematuria / deranged renal function or active sedimentson urine microscopy. 3) Steroid resistant nephrotic syndrome in children (patients not responding to steroidin eight weeks time) and 4) Children with nephrotic syndrome who were not tolerant of steroid therapy orwere considered for immunosuppressive drugs.RESULT: A total of 155 renal biopsies were done. Out of these 90 were male patients and 65 were females.The most common histopathological lesion among children population was minimal change disease(42.66%) followed by focal segmental glomerulosclerosis (25.33%) and membranous GN (16.0%). Weobserved that nephrotic range proteinuria was most prevalent in minimal change disease and membranousGN followed by focal segmental glomerulosclerosis. While non-nephrotic range proteinuria was mostlyseen in patients with membranoprolifirative GN.CONCLUSION: In paediatric population, minimal change disease is the most common encounteredglomerulopathy, followed by focal segmental glomerulosclerosisand membranous GN.KEY WORDS: Nephrotic syndrome, Renal biopsy, Proteinuria, Glomerulopathy

Minimal change disease

2018 ◽  
Author(s):  
Patrick Niaudet ◽  
Alain Meyrier
Keyword(s):  
Differential Diagnosis ◽  
Nephrotic Syndrome ◽  
Renal Biopsy ◽  
Minimal Change Disease ◽  
Minimal Change ◽  
Direct Effects ◽  
Glomerular Filtration Barrier ◽  
Common Cause ◽  
Filtration Barrier ◽  
Steroid Responsiveness

Minimal change disease is the most common cause of nephrotic syndrome in childhood but is not rare in adults. The factors altering permeability of the glomerular filtration barrier are not known, but podocyte structure is significantly altered in the condition and it seems certain that this cell is the target of whatever factors are responsible for the condition. It is still not clear that it is immunologically mediated and many of the agents used to treat it have direct effects on the podocyte. The differential diagnosis includes any other disease causing nephrotic syndrome, and a renal biopsy narrows this down. In children, steroid unresponsiveness is often used as a diagnostic test, and consideration of genetic or other pathologies reserved for patients who show no or poor steroid responsiveness.

scholarly journals Primary Nephrotic Syndrome and Risks of End-Stage Kidney Disease, Cardiovascular Events, and Death: The Kaiser Permanente Nephrotic Syndrome Study

2021 ◽  
pp. ASN.2020111583
Author(s):  
Alan Go ◽  
Thida Tan ◽  
Glenn Chertow ◽  
Juan Ordonez ◽  
Dongjie Fan ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Kidney Disease ◽  
Membranous Nephropathy ◽  
Minimal Change Disease ◽  
Cardiovascular Outcomes ◽  
Minimal Change ◽  
End Stage Kidney Disease ◽  
Kaiser Permanente ◽  
Primary Nephrotic Syndrome ◽  
End Stage

Background Few population-based data exist about adults with primary nephrotic syndrome. Methods To evaluate kidney, cardiovascular, and mortality outcomes in adults with primary nephrotic syndrome, we identified adults within an integrated health care delivery system (Kaiser Permanente Northern California) with nephrotic-range proteinuria or diagnosed nephrotic syndrome between 1996-2012. Nephrologists reviewed medical records for clinical presentation, laboratory findings, and biopsy results to confirm primary nephrotic syndrome and assigned etiology. We identified a 1:100 time-matched cohort of adults without diabetes, diagnosed nephrotic syndrome, or proteinuria as controls to compare rates of end-stage kidney disease (ESKD), cardiovascular outcomes, and death through 2014, using multivariable Cox regression. Results We confirmed 907 cases of primary nephrotic syndrome (655 definite and 252 presumed cases of focal segmental glomerulosclerosis [FSGS, 40%], membranous nephropathy [40%], and minimal change disease [20%]). Mean age was 49 years; 43% were women. Adults with primary nephrotic syndrome had higher adjusted rates of ESKD (adjusted hazard ratio [aHR], 19.63; 95% confidence interval [95% CI], 12.76 to 30.20), acute coronary syndrome (aHR 2.58; 95% CI, 1.89 to 3.52), heart failure (aHR 3.01; 95%CI, 2.16 to 4.19), ischemic stroke (aHR 1.80; 95%CI,1.06 to 3.05), venous thromboembolism (aHR 2.56; 95%CI, 1.35 to 4.85), and death (aHR 1.34; 95%CI, 1.09 to 1.64) versus controls. Excess ESKD risk was significantly higher for FSGS and membranous nephropathy than for presumed minimal change disease. The three etiologies of primary nephrotic syndrome did not differ significantly in terms of cardiovascular outcomes and death. Conclusions Adults with primary nephrotic syndrome experience higher adjusted rates of ESKD, cardiovascular outcomes, and death, with significant variation by underlying etiology in risk for developing ESKD.

MO1021HYPERTENSION IN CHILDHOOD MINIMAL CHANGE DISEASE: IGNORED, MISSED OR UNDER-DIAGNOSED?

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Sourabh Sharma ◽  
Neha Sharma
Keyword(s):  
Body Mass Index ◽  
Nephrotic Syndrome ◽  
Family History ◽  
Body Mass ◽  
Minimal Change Disease ◽  
Angiotensin Receptor Blockers ◽  
Tertiary Care ◽  
Minimal Change ◽  
Primary Nephrotic Syndrome ◽  
Steroid Dependent

Abstract Background and Aims Minimal change disease (MCD) is most common form of primary nephrotic syndrome (76.6% as per ISKDC) in children aged 1 to 10 years. As per current literature, blood pressure (BP) is usually normal in childhood MCD while in adults, 50% MCD cases are hypertensive. We hypothesized that hypertension is prevalent in childhood MCD also and most of cases are missed or under-diagnosed due to lack of BP monitoring, inappropriate BP cuff size (larger cuff will inaccurately show lower BP; cuff should cover 75% to 80% of arm circumference between antecubital fossa and axilla) or lack of knowledge about childhood hypertension criteria (systolic or diastolic BP> 95th percentile for age on ≥2 clinical visits at least 1 week apart). Method This cross-sectional study was performed from March 2018 to December 2020 at a tertiary care centre in India. Newly diagnosed and relapses of primary nephrotic syndrome (presumed MCD) in children aged 1 to 10 years were included in the study. All cases were subjected to careful BP monitoring and charting using appropriate BP cuff, while child is calm and relaxed, in quiet room with comfortable temperature and empty bladder. Three measurements were taken at 1 minute interals and taking average of last 2 measurements. Percentile charts for age and height were followed. Results fifty four cases of childhood MCD were studied. Thirty six cases (66.67%) were male. Mean age was 5.48 years (SD ±2.31). Thirty two cases (59.26%) were found to be hypertensive. Fourteen cases (43.75%) were relapses. Seven cases (21.87%) were steroid resistant nephrotic syndrome while three cases were steroid dependent. Five cases were already on calcineurin inhibitors when diagnosed of hypertension. There was family history of hypertension in 9 cases diagnosed of hypertension (p value 0.77). There was no correlation between occurrence of hypertension and degree of proteinuria, hypoalbuminemia or body mass index. All hypertensives were managed with angiotensin receptor blockers and regularly followed-up. Conclusion Results of our study are contrary to traditional belief that hypertension is not common in childhood MCD. Significant number of cases are hypertensive. Correct BP measurement and interpretation is necessary in each childhood MCD case. Its occurrence is not correlated with family history or degree of proteinuria, hypoalbuminemia or body mass index.

scholarly journals Rituximab use in adult glomerulopathies and its rationale

2020 ◽  
Vol 42 (1) ◽  
pp. 77-93
Author(s):  
Joana Eugénio Santos ◽  
David Fiel ◽  
Ricardo Santos ◽  
Rita Vicente ◽  
Rute Aguiar ◽  
...  
Keyword(s):  
End Stage Renal Disease ◽  
Membranoproliferative Glomerulonephritis ◽  
Minimal Change Disease ◽  
Minimal Change ◽  
Class Iii ◽  
Randomized Controlled ◽  
Remission Period ◽  
Steroid Dependent ◽  
Stage Renal Disease ◽  
End Stage

Abstract Glomerulopathies are one of the leading causes of end-stage renal disease. In the last years, clinical research has made significant contributions to the understanding of such conditions. Recently, rituximab (RTX) has appeared as a reasonably safe treatment. The Kidney Disease: Improving Global Outcomes guidelines (KDIGO) recommended RTX only as initial treatment in antineutrophil cytoplasm antibody associated vasculitis (AAV) and in non-responders patients with lupus nephritis (LN), but these guidelines have not been updated since 2012. Nowadays, RTX seems to be at least as effective as other immunosuppressive regimens in idiopathic membranous nephropathy (IMN). In minimal-change disease, (MCD) this drug might allow a long-lasting remission period in steroid-dependent or frequently relapsing patients. Preliminary results support the use of RTX in patients with pure membranous LN and immunoglobulin-mediated membranoproliferative glomerulonephritis (MPGN), but not in patients with class III/IV LN or complement-mediated MPGN. No conclusion can be drawn in idiopathic focal segmental glomerulosclerosis (FSGS) and anti-glomerular basement membrane antibody glomerulonephritis (anti-GBM GN) because studies are small, heterogeneous, and scarce. Lastly, immunosuppression including RTX is not particularly useful in IgA nephropathy. This review presents the general background, outcomes, and safety for RTX treatment in different glomerulopathies. In this regard, we describe randomized controlled trials (RCTs) performed in adults, whenever possible. A literature search was performed using clinicaltrials.gov and PubMed.

scholarly journals Case Report: Novel Dietary Supplementation Associated With Kidney Recovery and Reduction in Proteinuria in a Dialysis Dependent Patient Secondary to Steroid Resistant Minimal Change Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Rasheed A. Gbadegesin ◽  
Loren P. Herrera Hernandez ◽  
Patrick D. Brophy
Keyword(s):  
Nephrotic Syndrome ◽  
Kidney Disease ◽  
Minimal Change Disease ◽  
Minimal Change ◽  
Steroid Resistance ◽  
Small Subset ◽  
Disease Course ◽  
End Stage Kidney Disease ◽  
Steroid Resistant ◽  
End Stage

Minimal change disease (MCD) is the most common cause of nephrotic syndrome worldwide. For decades, the foundation of the treatment has been corticosteroids. However, relapse rate is high and up to 40% of patients develop frequent relapsing/steroid dependent course and one third become steroid resistant. This requires treatment with repeated courses of corticosteroids, and second and third line immunomodulators increasing the incidence of drug related adverse effects. More recently, there have been reports of a very small subset of Nephrotic Syndrome (NS) patients who are initially steroid sensitive and later become secondarily steroid resistant. The disease course in this small subset is often protracted leading ultimately to end stage kidney disease requiring dialysis or kidney transplantation. Unfortunately, patients with this disease course do not do well post transplantation because 80% of them will develop disease recurrence that will ultimately lead to graft failure. Few approaches have been tried over many years to reduce the frequency of relapses, and steroid dependence and there is absolutely no therapeutic intervention for patients who develop secondary steroid resistance. Nonetheless, their therapeutic index is low, evidencing the need of a safer complementary treatment. Several hypotheses, including an oxidative stress-mediated mechanism, and immune dysregulation have been proposed to date to explain the underlying mechanism of Minimal Change Disease (MCD) but its specific etiology remains elusive. Here, we report a case of a 54-year-old man with steroid and cyclosporine resistant MCD. The patient rapidly progressed to end stage kidney disease requiring initiation of chronic dialysis. Intradialytic parenteral nutrition (IDPN), albumin infusion along with a proprietary dietary supplement, as part of the supportive therapy, led to kidney function recovery and complete remission of MCD without relapses.

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