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.

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