Glomerular diseases.ppt

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.