KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases

Kidney International, Год журнала: 2021, Номер 100(4), С. S1 - S276

Опубликована: Сен. 20, 2021

The Kidney Disease: Improving Global Outcomes (KDIGO) 2021 Clinical Practice Guideline for the Management of Glomerular Diseases is an update to KDIGO 2012 guideline on topic. aim assist clinicians caring individuals with glomerular disease, both adults and children. scope includes various diseases, including IgA nephropathy (IgAN) vasculitis (IgAV), membranous nephropathy, nephrotic syndrome in children, minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), infection-related glomerulonephritis (GN), antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, lupus nephritis, anti-glomerular basement membrane (anti-GBM) GN. In addition, this will be first address subtype complement-mediated diseases. Each chapter follows same format providing guidance related diagnosis, prognosis, treatment, special situations. goal generate a useful resource patients by actionable recommendations valuable infographics based rigorous formal systematic literature review. Another propose research areas where there are gaps knowledge. targets broad audience treating while being mindful implications policy cost. Development followed explicit process evidence Treatment approaches reviews synthesis relevant studies, appraisal quality strength “Grading Recommendations Assessment, Development, Evaluation” (GRADE) approach. Limitations discussed, future also presented.

Язык: Английский

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Podocytopathies

Nature Reviews Disease Primers, Год журнала: 2020, Номер 6(1)

Опубликована: Авг. 13, 2020

Язык: Английский

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Management and treatment of glomerular diseases (part 2): conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Kidney International, Год журнала: 2019, Номер 95(2), С. 281 - 295

Опубликована: Янв. 18, 2019

In November 2017, the Kidney Disease: Improving Global Outcomes (KDIGO) initiative brought a diverse panel of experts in glomerular diseases together to discuss 2012 KDIGO glomerulonephritis guideline context new developments and insights that had occurred over years since its publication. During this Controversies Conference on Glomerular Diseases, group examined data disease pathogenesis, biomarkers, treatments identify areas consensus controversy. This report summarizes discussions primary podocytopathies, lupus nephritis, anti-neutrophil cytoplasmic antibody–associated complement-mediated kidney diseases, monoclonal gammopathies renal significance. The published first ever 2012.1Kidney Glomerulonephritis Work GroupKDIGO clinical practice for glomerulonephritis.Kidney Int Suppl. 2012; 2: 139-274Google Scholar Since then our understanding pathogenesis has markedly advanced, diagnostic biomarkers have entered arena, many therapies been assessed trials. Therefore, conference consisting about 100 from various disciplines (nephrology, pathology, rheumatology, pediatrics) organizations (academia, pharmaceutical industry) was convened 17–19, 2017. goals were evaluate progress made evaluation management assess continuing gaps knowledge, existing recommendations should be revisited next update. attendees especially encouraged outline most controversial aspects diseases. second 2 reports covers nephritis (LN), antibody (ANCA)-associated Each disease-specific working asked consider terminology, treatment, future studies. Taken together, these summaries will lay basis updating process began August 2018. terms "minimal change disease" (MCD) "focal segmental glomerulosclerosis" (FSGS) remain relevant. Although there may pathophysiologic overlap between MCD FSGS, presence focal sclerosis by light microscopy prognostic importance. To discriminate FSGS biopsy, at least 20 glomeruli are needed, biopsies performed soon after diagnosis only show MCD, but patients later develop FSGS.2Corwin H.L. Schwartz M.M. Lewis E.J. importance sample size interpretation biopsy.Am J Nephrol. 1988; 8: 85-89Google However, children, biopsy is not usually respond prednisone treatment. Response treatment timing relapses allows classification childhood nephrotic syndrome.3Vivarelli M. Massella L. Ruggiero B. et al.Minimal disease.Clin Am Soc 2017; 12: 332-345Google There designations "steroid-sensitive" "steroid-resistant" syndrome clinically useful descriptions children steroid-sensitive idiopathic syndromes MCD. therapy often more value than histology. "primary/idiopathic FSGS" reserved caused as yet unknown permeability factors. Patients with genetic, adaptive (in setting reduced nephron mass), drug-induced, viral-induced designated primary.4Rosenberg A.Z. Kopp J.B. Focal glomerulosclerosis.Clin 502-517Google Primary characterized acute-onset heavy proteinuria diffuse podocyte foot effacement histologically. Other subtypes typically modest effacement.5De Vriese A.S. Sethi S. Nath K.A. al.Differentiating primary, secondary adults: clinicopathologic approach.J 2018; 29: 759-774Crossref Scopus (127) Google Further efforts warranted better define subgroups their presumed pathogenesis. A role dysfunctional T cells proposed 40 ago.6Shalhoub R.J. Pathogenesis lipoid nephrosis: disorder T-cell function.Lancet. 1974; 556-560Google More recently, B become evident, supported efficacy immunoadsorption B-cell depletion inducing remission.3Vivarelli Thus far none reported circulating factor candidates independently validated FSGS.7Maas Deegens J.K. Wetzels J.F. Permeability factors syndrome: historical perspectives lessons future.Nephrol Dial Transplant. 2014; 2207-2216Google Soluble urokinase-type plasminogen activator receptor novel biomarker chronic disease, does appear or represent FSGS.8Hayek S.S. Sever Ko Y.A. al.Soluble urokinase disease.N Engl Med. 2015; 373: 1916-1925Google Cardiotrophin-like cytokine-1, member interleukin 6 cytokine family, candidate factor. cytokine-1 identified plasma found decrease nephrin expression culture. recurrent concentration up times normal subjects. Angiopoietin-like-4, secreted glycoprotein, highly upregulated serum podocytes experimental models human disease. relevant potential syndrome.9Clement L.C. Avila-Casado C. Mace al.Podocyte-secreted angiopoietin-like-4 mediates glucocorticoid-sensitive syndrome.Nat 2011; 17: 117-122Google Scholar, 10McCarthy E.T. Sharma Savin V.J. Circulating 2010; 5: 2115-2121Google It suggested MCD/FSGS mediated CD80 (B7-1) induced an innocuous event such infection.11Shin J.I. Kronbichler A. Rituximab syndrome.Lancet. 385: 225-226Google overexpression could confirmed.12Novelli R. Gagliardini E. al.Any B7-1 FSGS?.Am Physiol Renal Physiol. 2016; 310: F335-F341Scopus (32) parietal epithelial virtually all histological types lesions also proposed.13Shankland S.J. Smeets Pippin J.W. al.The emergence cell.Nat Rev 10: 158-173Google no ready use FSGS. subtype defined Columbia classification14D'Agati V.D. Fogo A.B. Bruijn J.A. al.Pathologic glomerulosclerosis: proposal.Am Dis. 2004; 43: 368-382Google support decision making help anticipating response prognosis,15D'Agati Alster J.M. Jennette J.C. al.Association histologic variants trial presenting features outcomes.Clin 2013; 399-406Google it specific underlying mechanisms. Immunostaining specimens cell activation markers improve sensitivity detecting sclerotic when distinguishing MCD.16Smeets Stucker F. J. al.Detection activated tuft distinguishes early glomerulosclerosis minimal disease.Am Pathol. 184: 3239-3248Google Proteomic analysis provide additional insights. Genetic testing pediatric adult controversial, considered congenital infantile forms (children <1 year age) less age steroid-resistant syndrome, associated other syndromic features, familial syndrome/FSGS.17Gbadegesin R.A. Winn M.P. Smoyer W.E. syndrome—challenges opportunities.Nat 9: 179-184Google 18Lovric Ashraf Tan W. al.Genetic how?.Nephrol 31: 1802-1813Google 19Sadowski C.E. Lovric al.A single-gene cause 29.5% cases syndrome.J 26: 1279-1289Google Adding controversy perform genetic testing, single gene mutations 30% under 25.18Lovric Testing target genes based patient characteristics contemporary knowledge. high-risk apolipoprotein L1 genotypes development still investigation agreed insufficient using information guide decisions. inclusion stratification Biospecimens routinely collected, consented analysis. Ethical issues addressed before recommending analyses. While immunomodulatory first-line primary/idiopathic factor, blood pressure control correction abnormal hemodynamics, hypertension (e.g., FSGS), interventions. causative controversial. Rare varying degrees remission reflect nonimmune modulating effects therapies.20Trautmann Schnaidt Lipska-Zietkiewicz B.S. al.Long-term outcome children.J 28: 3055-3065Google Following identification mutations, include known directed coenzyme Q-10, vitamin B12 where applicable),18Lovric antiproteinuric therapy, prompt discontinuation immunosuppressive those signal response.21Trautmann Bodria Ozaltin al.Spectrum children: PodoNet registry cohort.Clin 592-600Google Because ∼80% incident remaining patients, some corticosteroid challenge treating corticosteroids first, except younger 9 10 months age. Due increased incidence age, consideration older 12 prior recommended. recent randomized controlled trials do steroid exposure beyond 8 weeks.22Teeninga N. Kist-van Holthe J.E. van Rijswijk al.Extending prednisolone reduce 24: 149-159Google 23Sinha Saha Kumar initial 3 did significantly influence course illness syndrome.Kidney Int. 87: 217-224Google 24Yoshikawa Nakanishi K. Sako multicenter indicates two inferior six-month treatment.Kidney 225-232Google minimum duration required resistance. recommended weeks defining reached, need globally accepted definition "steroid resistance" comparability recognized. low-dose daily alternate day dosing maintaining relapsing promising.25Yadav Sinha Hari P. Bagga Efficacy versus frequently (FRNS): open-label (RCT). Abstract FP-S25-09.Pediatr 1752Google Therapy alternative agents syndrome. cyclophosphamide (CYC), levamisole, mycophenolate mofetil (MMF), calcineurin inhibitors (CNIs), rituximab (RTX), precise order well determined.26Iijima Nozu al.Rituximab childhood-onset, complicated, steroid-dependent multicentre, double-blind, randomised, placebo-controlled trial.Lancet. 384: 1273-1281Google Data emerging RTX direct action confirmed, supporting RTX's mechanism action.27Kim A.H. Chung J.J. Akilesh al.B cell-derived IL-4 acts induce effacement.JCI Insight. (pii:81836)Google Post hoc analyses suggest targeting higher area serum/plasma concentration-time curves MMF result similar numbers CNIs, needs confirmed trials.28Gellermann Weber Pape al.Mycophenolate cyclosporin 1689-1697Google Nephrotic high risk infection regardless immunosuppression. provides regarding vaccinations highlight hepatitis screening vaccination, receiving depleting therapies.29Masse V. Al Jijakli Genet al.Screening virus infusion: We must better!.Blood. 124 (Available at:): 2754http://www.bloodjournal.org/content/124/21/2754Date accessed: March 15, 2018Google Vaccination against meningococci included expert opinion. adults, 16 high-dose felt given toxicity. combination lower doses insufficient. CNIs CYC second-line adults although evidence observational only. recommendation second- third-line treatments, respectively, maintained. Randomized underway investigate (Efficacy Comparison Continued Corticosteroid Treatment Idiopathic Syndrome; NCT03298698) inhibitor abatacept, podocytes, (Pilot Study Evaluate Safety Abatacept Adults Children Years Older With Excessive Loss Protein Urine Either Segmental Glomerulosclerosis Minimal Change Disease; NCT02592798). important distinguish which investigational effective. Immunologic focus FSGS; antifibrotic recruit Recommendations outlined Supplementary Table S1. term "membranoproliferative" (GN) retains descriptor injury, increasing C3 glomerulopathy (C3G) significance (MGRS) (paraprotein-associated diseases) illustrate nomenclature injury pattern. Additionally, histology etiologies always membranoproliferative GN. updated guidelines emphasize approach GN considers both pathobiology histology, 1.30Sethi Haas Markowitz G.S. al.Mayo Clinic/Renal Pathology Society Consensus pathologic classification, diagnosis, reporting GN.J 27: 1278-1287Google Over time, greater scheme lead elimination distinct category guidelines. following discussion highlights controversies exist within framework, including issue overlapping mechanisms, conundrum common inevitable fact "idiopathic" nature.31Fervenza F.C. Glassock glomerulonephritis: exist?.Nephrol 4288-4294Google ScholarTable 1A pathogenesis-based glomerulonephritisAdapted S, M, GS, al. Mayo 2016;27:1278–1287,30Sethi permission. Copyright © 2016 American Nephrology.Pathogenic typeDisease examplesImmune complex glomerulonephritisIgA nephropathyLupus nephritisFibrillary (polyclonal/DNAJB9-positive subtype)Infection-associated glomerulonephritisMixed (types II III) cryoglobulinemic glomerulonephritisPauci-immune glomerulonephritisANCA-associated vasculitisANCA-negative pauci-immune glomerulonephritisAntiglomerular basement membrane diseaseMonoclonal Ig-associated glomerulonephritisMonoclonal Ig deposition (LCDD, HCDD, LHCDD)Proliferative depositsMonoclonal (type I) glomerulonephritisImmunotactoid glomerulopathyFibrillary (monoclonal subtype)Complement-mediated glomerulonephritisC3 glomerulonephritisDense deposit diseaseANCA, antibody; DNAJB9, DNA homolog subfamily 9; chain disease; LCDD, LHCDD, Open table tab ANCA, nonroutine techniques, pronase unmask hidden epitopes,32Nasr S.H. Galgano al.Immunofluorescence pronase-digested paraffin sections: valuable salvage technique biopsies.Kidney 2006; 70: 2148-2151Google 33Larsen C.P. Ambuzs Bonsib S.M. al.Membranous-like masked IgG kappa deposits.Kidney 86: 154-161Google 34Messias N.C. Walker P.D. Larsen Paraffin immunofluorescence pathology laboratory: technique.Mod 854-860Google 35Larsen Messias al.Membranoproliferative monotypic immunoglobulin 88: 867-873Google C4d staining C3G Ig-mediated postinfectious GN,36Sethi Nasr De al.C4d tool proliferative 2852-2859Google protein fibrillary GN37Andeen N.K. Yang H.Y. Dai D.F. al.DnaJ putative autoantigen 231-239Google 38Dasari Alexander Vrana heat shock family 51-56Google possibly Most techniques verification. complement activation, and/or degradation. Drivers reviewed consensus39Pickering M.C. D'Agati Nester C.M. al.C3 glomerulopathy: report.Kidney 84: 1079-1089Google reports.40Goodship T.H. Cook H.T. Fakhouri al.Atypical hemolytic uremic conclusions "Kidney Outcomes" Conference.Kidney 91: 539-551Google generally animal well-described scenarios, matter practicality continues difficult substantiate causal either nucleotide changes nephritic majority cases.41Servais Noel L.H. Roumenina L.T. al.Acquired abnormalities play critical dense glomerulopathies.Kidney 82: 454-464Google 42Iatropoulos Daina Curreri al.Cluster identifies pathogenetic patterns glomerulopathies/immune complex-mediated 283-294Google Furthermore, confounded heterogeneity criteria used diagnosis. Addressing targeted anticomplement available. summarized recently.40Goodship utility soluble C5b-9 levels predicting remains unclear. Controversy extended assessment serial requires further study. paraproteins received attention.43Zand Kattah Fervenza gammopathy: case series.Am 62: 506-514Google outlined,40Goodship derived mostly retrospective series. An knowledge gap absence robust natural history. Current empirically extrapolated optimal inhibiting definable pathways (inflammation terminal activity) available therapeutics (antiproliferative blockers). active shown promise series,44Avasare R.S. Canetta P.A. Bomback steroids series.Clin 13: 406-413Google 45Rabasco Cavero T. Roman al.Effectiveness 1153-1160Google effective third series severe baseline disease.46Caliskan Y. Torun E.S. Tiryaki T.O. al.Immunosuppressive really effective?.Am 46: 96-107Google For gammopathy, superior hematologic rates, survival, treated clone-directed chemotherapy compared conservative treatment.47Chauvet Fremeaux-Bacchi Petitprez al.Treatment improves gammopathy-associated glomerulopathy.Blood. 129: 1437-1447Google Preclinical studies elucidated paraprotein-associated example, truncated lacks constant domain (CH1 deletion).48Vignon Cohen Faguer related IgA 720-728Google 49Bonaud Bender Touchard G. mouse model recapitulating evidences relevance proteasome therapy.Blood. 126: 757-765Google Specific physiochemical properties explain tropism kidney.50Bridoux Javaugue al.Unravelling immunopathological mechanisms implications management.Kidney 423-434Google clone meet multiple myeloma (i.e., MGRS), can bone marrow.50Bridoux MGRS, pathogenic Igs clones. Targeting clones outcomes,47Chauvet 50Bridoux 51Cohen Royer al.Bortezomib produces hig

Язык: Английский

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New ‘Antigens’ in Membranous Nephropathy

Journal of the American Society of Nephrology, Год журнала: 2020, Номер 32(2), С. 268 - 278

Опубликована: Дек. 30, 2020

Membranous nephropathy (MN) occurs due to deposition of immune complexes along the subepithelial region glomerular basement membrane. Two previously identified target antigens for complexes, PLA2R (identified in 2009) and THSD7A (in 2014), account approximately 60% all MN, both primary secondary. In remaining were unknown. Use laser microdissection mass spectrometry enabled identification new “antigens.” This approach led four novel types MN: exotosin 1 (EXT1)– 2 (EXT2)–associated NELL1-associated Sema3B-associated PCDH7-associated MN. Each these represents a distinct disease entity, with different clinical pathologic findings. this review, structure proteins findings MN are discussed. The role accurate diagnosis cannot be overemphasized. Finally, any classification should made on basis that detected. Further studies required understand pathophysiology, response treatment, outcomes MNs.

Язык: Английский

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Focal Segmental Glomerulosclerosis: State-of-the-Art and Clinical Perspective

˜The œNephron journals/Nephron journals, Год журнала: 2020, Номер 144(9), С. 413 - 427

Опубликована: Янв. 1, 2020

Focal segmental glomerulosclerosis (FSGS) is a histological pattern of glomerular injury, rather than single disease, that caused by diverse clinicopathological entities with different mechanisms injury the podocyte as principal target lesion, leading to characteristic sclerotic lesions in parts (i.e., focal) some segmental) glomeruli. The lesion FSGS has shown an increasing prevalence over past few decades and considered most common cause ESKD. Primary FSGS, which usually presents nephrotic syndrome, thought be circulating permeability factors have main role foot process effacement. Secondary forms include maladaptive secondary hyperfiltration such obesity or cases loss nephron mass, virus-associated drug-associated can result direct injury. Genetic increasingly been recognized careful evaluation patients atypical primary should performed exclude genetic causes. Unlike do not respond immunosuppression tend recur after kidney transplantation. Distinguishing from causes prognostic significance crucial for appropriate management. In this review, we examine pathogenesis, clinical approach distinguish between causes, current recommendations management FSGS.

Язык: Английский

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Therapeutic trials in adult FSGS: lessons learned and the road forward

Nature Reviews Nephrology, Год журнала: 2021, Номер 17(9), С. 619 - 630

Опубликована: Май 20, 2021

Язык: Английский

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Ion channels and channelopathies in glomeruli

Physiological Reviews, Год журнала: 2022, Номер 103(1), С. 787 - 854

Опубликована: Авг. 25, 2022

An essential step in renal function entails the formation of an ultrafiltrate that is delivered to tubules for subsequent processing. This process, known as glomerular filtration, controlled by intrinsic regulatory systems and paracrine, neuronal, endocrine signals converge onto cells. In addition, characteristics fluid flow, such filtration rate fraction, play important role determining blood flow rest kidney. Consequently, disease processes initially affect glomeruli are most likely lead end-stage kidney failure. The cells comprise filter, especially podocytes mesangial cells, express many different types ion channels regulate aspects cell cellular responses local environment, changes capillary pressure. Dysregulation channels, TRPC6, can devastating diseases, a number including TRPC5, various ionotropic receptors, promising targets drug development. review discusses structure processes. It also describes plasma membrane have been identified physiological pathophysiological contexts which they operate, pathways regulated dysregulated. contributions these processes, focal segmental glomerulosclerosis (FSGS) diabetic nephropathy, well development drugs target discussed.

Язык: Английский

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Current understanding of the molecular mechanisms of circulating permeability factor in focal segmental glomerulosclerosis

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Сен. 19, 2023

The pathogenetic mechanisms underlying the onset and post-transplant recurrence of primary focal segmental glomerulosclerosis (FSGS) are complex remain yet to be fully elucidated. However, a growing body evidence emphasizes pivotal role immune system in both initiating perpetuating disease. Extensive investigations, encompassing experimental models patient studies, have implicated T cells, B complement as crucial actors pathogenesis FSGS, with various molecules being proposed potential “circulating factors” contributing disease its post kidney-transplantation. In this review, we critically assessed existing literature identify essential pathways for comprehensive characterization FSGS. Recent discoveries shed further light on intricate interplay between these mechanisms. We present an overview current understanding engagement distinct cells FSGS while highlighting critical knowledge gaps that require attention. A thorough holds noninvasive biomarkers can accurately patients at high risk recurrence. Such pave way development targeted personalized therapeutic approaches management

Язык: Английский

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Management of adult patients with podocytopathies: an update from the ERA Immunonephrology Working Group

Nephrology Dialysis Transplantation, Год журнала: 2024, Номер 39(4), С. 569 - 580

Опубликована: Фев. 10, 2024

ABSTRACT The histopathological lesions, minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are entities without immune complex deposits which can cause podocyte injury, thus frequently grouped under the umbrella of podocytopathies. Whether MCD FSGS may represent a spectrum same remains matter conjecture. Both require repeated high-dose glucocorticoid therapy with alternative immunosuppressive treatments reserved for relapsing or resistant cases response rates variable. There is an unmet need to identify patients who should receive therapies as opposed those would benefit from supportive strategies. Therapeutic trials focusing on scarce, evidence used 2021 Kidney Disease: Improving Global Outcomes (KDIGO) guideline management glomerular diseases largely stems observational pediatric trials. In FSGS, differentiation between primary forms underlying genetic variants secondary further complicates trial design. This article provides perspective Immunonephrology Working Group (IWG) European Renal Association (ERA) discusses KDIGO Clinical Practice Guideline Management Glomerular Diseases in context recently published evidence, special emphasis role rituximab, cyclophosphamide, treatment options ongoing clinical field.

Язык: Английский

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Understanding the podocyte immune responses in proteinuric kidney diseases: from pathogenesis to therapy

Frontiers in Immunology, Год журнала: 2024, Номер 14

Опубликована: Янв. 15, 2024

The glomerular filtration barrier, comprising the inner layer of capillary fenestrated endothelial cells, outermost podocytes, and basement membrane between them, plays a pivotal role in kidney function. Podocytes, terminally differentiated epithelial are challenging to regenerate once injured. They essential for maintaining integrity barrier. Damage resulting from intrinsic or extrinsic factors, leads proteinuria early stages eventually progresses chronic disease (CKD). Immune-mediated podocyte injury is primary pathogenic mechanism proteinuric diseases, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, lupus nephritis with involvement. An extensive body evidence indicates that podocytes not only contribute significantly maintenance barrier serve as targets immune responses but also exhibit cell-like characteristics, participating both innate adaptive immunity. play mediating represent potential therapeutic CKD. This review aims systematically elucidate mechanisms various lesions provide an overview recent advances immunotherapy. It offers valuable insights deeper understanding identification new targets, has significant implications future clinical diagnosis treatment podocyte-related disorders.

Язык: Английский

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