Nephrotic range proteinuria –
early morning urine protein is 3+/4+ ,
Spot protein/creatinine ratio >2 mg/mg,
urine albumin excretion >40 mg/m2 /hr (on a timed sample).
Serum albumin < 2.5 gm/dL
Hyperlipidemia (serum cholesterol >200 mg/dL)
Oedema +
PATHOGENESIS
The extent of immunological dysfunction, (T cell dysfunction : corticosteroids’, Cyclosporine , and B cell dysfunction responsive to Rituximab ) and its relationship with proteins of the slit diaphragm and the podocyte cytoskeleton, is unclear. A unifying hypothesis that combines the immunological perturbations with abnormal function at the level of the slit diaphragm is lacking.
PATHOLOGY :
SSNS : over 80 % patients, the histology shows insignificant glomerular abnormalities on light microscopy, termed minimal change disease , 5–10 % cases FSGS
SRNS : minimal change disease and FSGS in 30–40 % patients each,
Indications for Renal Biopsy
(i) age at onset <1 y or >16 y,
(ii) gross hematuria, persistent microscopic hematuria or low serum C3;
(iii) renal failure, not attributable to hypovolemia;
(iv) suspected secondary causes; and
(v) sustained severe hypertension.
AND (i)diagnosis of steroid resistance is made, (ii) therapy with calcineurin inhibitors is planned.
The specimen should be examined by light and immunofluorescence microscopy. Electron microscopy helps confirm the diagnosis of minimal change disease (MCD), and
early membranous nephropathy, membranoproliferative glomerulonephritis and Alport syndrome.
MANAGEMENT OF THE INITIAL EPISODE
•Prednisolone is given at a dose of 2 mg/kg per day (maximum 60 mg) in single or divided doses(?) for 6 wk, followed by 1.5 mg/kg (maximum 40 mg) as a single morning dose on alternate days for the next 6 wk. Therapy with corticosteroids is then stopped (?). • •Prolongation of initial steroid therapy for 12 wk or longer is associated with significantly reduced risk for subsequent relapses WITH increased risk of steroid adverse effects
THERAPY FOR RELAPSE
• •Relapses are often triggered by minor infections. Symptomatic therapy of infectious illness might result in remission of low grade (1+/2+) proteinuria. • •Prednisolone is given at a dose of 2 mg/kg/d (single or divided doses) until urine protein is negative or trace for three consecutive days (remission), and subsequently as a single morning dose of 1.5 mg/kg on alternate days for 4 wk, and then discontinued
FREQUENT RELAPSES AND STEROID DEPENDENCE
qLong Term, Alternate Day (LTAD) Steroids 0.3–0.7 mg/kg is given on alternate days for 9–18 mo. v Increasing the frequency of administration of prednisolone from alternate day to daily during minor infectious illnesses is effective in preventing infection precipitated relapses
