Click here to load reader
Upload
nagaraj-reddy
View
201
Download
6
Embed Size (px)
DESCRIPTION
entire description related to glomerular diseases
Citation preview
Dr. srikanth, M.D.
Previous lecture??
Nephritic syndromesDiscussed as three entitiesAcute nephritis- days to weeksRapidly progressive glomerlonephritis- weeks
to monthsChronic glomerulonephritis- months to years
EtiologyAcute nephritis/RPGNImmune complex GN
Poststreptococcal GN Group A beta-hemolytic streptococci (pharyngitis or impetigo), primarily in children
Lupus nephritis Cryoglobulinemia -hepatitis C infection Bacterial endocarditis IgA nephropathy & Henoch-Schönlein
purpura (HSP).Anti GBM/Goodpasture’s syndrome
• Circulating antibodies against type 4 collagen that damages the GBM and causes RPGN
Pauci-immune GN Idiopathic Microscopic polyangiitis Wegener’s granulomatosisRenal limited crescentic glomerulonephritis
Chronic nephritis Can be a consequence of virtually all of the major glomerulopathies
Signs and symptomsAcute nephritis
Oliguria (< 400 mL/day of urine) over days to weeks
Extracellular fluid volume expansion, edema, and hypertension
RPGN Renal failure develops over weeks to months in
association with variable oliguria, hypervolemia, edema, and hypertension.
Oliguria
Chronic nephritis
Often asymptomatic. Diagnosis typically is made in one of the following
circumstances: Evaluation for secondary causes of hypertension Routine urinalysis Evaluation of unexplained anemia, blood urea and
creatinine Following discovery of bilateral small kidneys on
abdominal imaging During a clinical exacerbation of GN triggered by
pharyngitis or other infections
What are the important ones?? Post streptococcalLupusBacterial endocarditisCryogloblinemiaWegener’sAnti GBM disease
Can you classify them based on immune complexes??
Post streptococcalPoststreptococcal GN
10 days after pharyngitis or 2 weeks after a skin infection (impetigo) with a nephritogenic strain of group A β-hemolytic streptococcus.
Classic clinical presentation is full-blown nephritic syndrome-oliguric acute renal failure. Most patients have milder disease.
Overt disease presents as gross hematuria (red or "smoky" urine), headache, and generalized symptoms such as anorexia, nausea, vomiting, and malaise.
Swelling of the renal capsule can cause flank or back pain.
Hypervolemia, edema, and hypertension. The antecedent streptococcal infection may
still be evident or may have resolved, either spontaneously or in response to antibiotic therapy
Most of the times- a clinical diagnosis. Investigations can help. (Now, what are they?? and how do I treat this???)
Lupus nephritis40-85% of SLE patientsVarying picture- asymptomatic proteinuria to full
blown nephriticPathogenesis is contributed by thrombotic
microangiopathy(??), in addition to Immune complex mediated nephritis(remember this??)
5 classes based on biopsy (I to V)
Cryoglobulinemia and bacterial endocarditis
Circullating immune complexes- deposited in the glomerulus.
Cryoglobulins- also have skin ulcers, arthralgia’s, fatigue, raynaud’s. HCV has been implicated. 50% have renal involvement
Bacterial endocarditis
Wegener’s
80% of the patients show renal involvement.Varies from indolent smoldering inflammation to
rapidly progressive renal failure.Upper & lower respirarory tract involvement
Anti GBM diseaseAutoimmunity
Anti GBM diseaseAntibodies to Col4A5Anti-GBM nephritis with lung hemorrhage (50–
70% of patients) is referred to as Goodpasture’s syndrome.
Presents with hematuria and rapidly progressive renal failure over weeks, with or without pulmonary hemorrhage.
When pulmonary hemorrhage occurs, it usually predates nephritis by weeks or months.
Mild dyspnea on exertion to life-threatening pulmonary hemorrhage.
hypertension is unusual
Investigations
BiochemistryUrea, creatinineC3, C4 levelsASO, Anti- DNAseUrine- RBC’s, sediment, protein.ANA, ANCA, HCVAnti- GBM antibodies.
Granular, Linear
Renal biopsy
Gold standardDelineates the problem to glomerulus,
tubulointerstitum.Identifies specific immunoglobulins- eg IgAImmunoflorescence
Treatment
Not a child’s play
TreatmentPost streptococcal- simple
Eliminate streptococcal infectonSupportive therapy with diuretics and anti
hypertensivesRarely need renal replacement therapyExcellent prognosis
Lupus nephritis- not so easy,needs biopsy.No Rx- normal biopsy results or only mesangial
deposits, these histologies portend an excellent prognosis.
Glucocorticoids and cyclophosphamide are the mainstays of therapy for patients with proliferative nephritis. Cyclophosphamide
IV pulsed cyclophosphamide has good efficacy and is less toxic. Initially monthly intravenous boluses of cyclophosphamide for 6 months.
Subsequent therapy is tailored to disease activity and typically involves dosing every 3–6 months for a total treatment period of 12–24 months.
Initial dose is 0.5 g/m2, with the dose increased gradually to a maximum of 1 g/m2 unless patients develop leukopenia or other side effects.
May be replaced with either azathioprine or mycophenolate.
Prednisone Start at 1 mg/kg per day and taper over the first
6 months to a maintenance dose of 5–10 mg/d for the duration of cyclophosphamide therapy.
High dose IV steroids to tide over the acute crisis.
Cryoglobulinemia- Glucocorticoids with/without cyclophosphamide
Wegener’s- CyclophosphamideAnti- GBM disease-Emergency plasmapheresis
daily or on alternate days until anti-GBM antibodies are no longer detected in the circulation (usually 1–2 weeks).
Prednisone (1 mg/kg per day) is started simultaneously, in combination with either cyclophosphamide or azathioprine to suppress new synthesis of anti-GBM antibodies. Early initiation of therapy is criticalRelapses are not unusual.