Glomérulopathies

Terminologie

• Lésion diffuse (tous les glomérules atteints) vs focale (<50% des glomérules atteints)
• Lésion globale (l'entier du glomérule) vs segmentaire (<50% du glomérule)
• Lésion proliférative, sclérosante, nécrosante

Résumé

	Syndrome néphritique	Syndrome néphrotique
Physiopathologie	Inflammation diffuse des glomérules = glomérulonéphrite	↑ perméabilité de la membrane basale glomérulaire
Protéinurie	< 3 g/24h	> 3 − 3,5 g/24h
Sérum		Albuminémie < 30 g/l Cholestérol sérique ↑ Hypercoagulabilité Risque infectieux ↑
Fonction rénale	Hématurie (microscopique ou macroscopique) Insuffisance rénale avec oligurie (inconstante et de degré variable)	Forme pure: pas d'insuffisance rénale organique
Clinique (OMI, HTA)	Triade de Volhard: HTA, hématurie, oedèmes	OMI
Sédiment urinaire	Erythrocytes dysmorphiques et/ou cylindres érythrocytaires

Syndrome néphritique

Glomérulonéphrite rapidement progressive

• Caractéristiques:
  1. at least a 50% decline in glomerular filtration rate over a short period (usually days to weeks) with
  2. pathology findings of extensive glomerular crescents
• Entités associées:
  • Vasculites ANCA positives (polyangéites microscopiques: Granulomatose de Wegener, Polyangéite microscopique)
  • Syndrome de Goodpasture (↓ anticorps anti-membrane basale glomérulaire)
  • Lupus érythémateux disséminé (LED)
  • ↓ Néphropathie à IgA (rare)

Glomérulonéphrite à anticorps anti-membrane basale

• Lung involvement (Goodpasture syndrome) occurs in >50% of patients
• Treatment for anti-GBM disease consists of plasmapheresis, pulse glucocorticoids (high doses of intravenous glucocorticoids over a short period of time) followed by oral prednisone, and cyclophosphamide.

Néphropathie à IgA

Synonyme: maladie de Berger

• Epidémiologie: maladie glomérulaire la plus répandue au monde
• Physiopathologie: dépôts mésangiaux d'IgA aberrants qui entraînent une inflammation locale, aboutissant à des lésions glomérulaires constituées, responsables d’une fuite de protéines et d’hématies dans l’urine<ref>RevMed
• Clinique: Recurrent gross hematuria, in which macroscopic hematuria occurs in the setting of an upper respiratory infection (synpharyngitic hematuria) is a common presentation in younger patients
• Diagnostic: biopsie
• Traitement:
  • Antiproteinuric therapy using an ACE inhibitor or angiotensin receptor blocker (ARB) is the hallmark for treating IgA nephropathy and remains the most proven therapy in slowing progression of the disease.
  • iSGLT-2, corticostéroïdes/budésonide, ...
• Suivi:
  • Protéinurie (cible <1g/24h), (suivi en % des érythrocytes glomérulaires)

Glomérulonéphrite post-infectieuse

• Diagnostic: Fraction C3 du complément abaissée dans 90% des cas, biopsie rénale à discuter
• Traitement: cause sous-jacente, glucocorticoïdes

Glomérulonéphrite membrano-proliférative

Type 1: forme à complexes immuns

• An immune-complex MPGN, with or without cryoglobulinemia, is the classic form of kidney involvement seen in patients with hepatitis C virus infection
• The more common pattern is immune-complex deposition with the presence of both immunoglobulin (IgG, IgM, and/or IgA) and complement (C1q and/or C3) on immunofluorescence, which infers that the classical pathway has been activated by an inciting cause or event that generally falls into one of three major categories: infectious, autoimmune, or malignancy associated. The most common is infectious, specifically infection with hepatitis C virus (HCV).

Syndrome néphrotique

Hyalinose segmentaire et focale

• Synonymes: glomérulosclérose focale et segmentaire (FSGS)
• Traitement non spécifique néphroprotecteur: IEC/ARA (protection de la fonction rénale), diurétique (contrôle de l'oedème) et hypolipémiant selon profil lipidique
• Traitement spécifique: glucocorticoïdes si protéinurie néphrotique et si FSGS primaire suspecté
  • Deuxième ligne: calcineurin inhibitors, mycophenolate mofetil, alkylating agents, and rituximab si absence de réponse aux glucocorticoïdes

Glomérulonéphrite extra-membraneuse

• Lésion principale: podocyte et membrane basale glomérulaire
• Mécanisme: auto-immun (complexes immuns et IgG in situ)
• Diagnostic: biopsie, dosage des anticorps anti-phospholipase A2 (PLA2)
• Traitement non spécifique néphroprotecteur: IEC/ARA (protection de la fonction rénale), diurétique (contrôle de l'oedème) et hypolipémiant selon profil lipidique
• Complications:
  • Thrombophilie (en particulier de la veine rénale) → In a large retrospective cohort of clotting complications in membranous glomerulopathy, >70% of the clots occurred within 2 years of diagnosis, and the risk of clotting markedly increased once albumin levels dropped below 2.8 g/dL (28 g/L) (OR, 2.53; P = 0.02, compared with albumin ≥2.8 g/dL [28 g/L]).

Forme primaire

• Patients with newly diagnosed primary forms of membranous glomerulopathy are usually observed for 6 to 12 months on conservative therapy (renin-angiotensin system blockade, cholesterol-lowering medication, and edema management) before initiating a course of immunosuppression for patients with persistent nephrotic-range proteinuria. The observation period allows patients a chance to achieve spontaneous remission, which occurs in approximately 30% within 1 to 2 years of diagnosis.
• Traitement immunosuppresseur (3 lignes):
  • Glucocorticoïdes et agent alkylant (cyclophosphamide: Endoxan)
  • Ciclosporine/tacrolimus
  • Rituximab

Forme secondaire

• associée au cancer (côlon, prostate), infections (hépatites B et C), maladies auto-immunes (lupus), médicaments (AINS, captopril)
• The initial step in the management of newly diagnosed membranous glomerulopathy is to evaluate for secondary forms of the disease, which account for approximately 25% of cases.

Néphropathie diabétique

• The hallmark clinical features include a proteinuric form of chronic kidney disease in a patient with long-standing diabetes mellitus and evidence of other (microvascular and/or macrovascular) complications of disease.
• cornerstone of treatment: improved glucose control, and blockade of the renin-angiotensin system (RAS) with an ACE inhibitor or ARB using the maximal tolerated dose.

Indications à la biopsie

The decision to pursue a kidney biopsy should be individualized for each patient, but, in general, a kidney biopsy appears justified for patients with two or more of the following four findings:

• hematuria,
• proteinuria >1000 mg/24 h,
• reduced kidney function (glomerular filtration rate <60 mL/min/1.73 m2),
• and/or positive serologies for systemic diseases with known potential for kidney involvement (for example, hepatitis B or C virus infection, systemic lupus erythematosus, and ANCA seropositivity).

kidney biopsy is not indicated in the setting of small echogenic kidneys <9 cm in size, which signifies chronic irreversible disease.

Références

• 2012: https://www.revmed.ch/RMS/2012/RMS-330/Proteinurie-rappel-physiologique-et-applications-pratiques