Primary nephrotic syndrome /idiopathic nephrotic syndrome Steroid resistant INS (SRNS) Steroid sensitive IN (SSNS) response to steroids has a high correlation with histological subtype and prognosis
PODOCYTE BIOLOGY Effacement of podocytes is now thought to be the primary pathology. -ve charge of the basement membrane is also important.
GENETICS. Nephrin Transmembrane protein encoded by NPHS 1 on chromosome 19.(FINISH type congenital NS. Podicin Encoded by NPHS 2 on chromosome 1. Autosomal recessive. Mutations in α-actinin-4, encoded by the gene ACTN4 on chromosome 19 and TRPC6 on chromosome 11, are associated with autosomal dominant forms of FSGS
Pathophysiology cont… Decreased plasma oncotic pressure may play a role in increased hepatic lipoprotein synthesis, as demonstrated by the reduction of hyperlipidemia in patients with INS receiving either albumin or dextran infusions Patients with nephrotic syndrome are at increased risk for thrombosis. Abnormalities described in INS include increased platelet activation and aggregation; elevation in factors V, VII, VIII, and XIII and fibrinogen; decreased antithrombin III, proteins C and S, and factors XI and XII; and increased activities of tissue plasminogen activator and plasminogen activator inhibitor-1. Decreased levels of Ig G and increased losses of factor B.
INVESTIGATIONS ESTABLISH nephrotic syndrome Nephrotic range proteinuria Hypoalbuminemia Hyperlipidemia Primary or secondary nephrotic syndromes If Primary, Whether in renal failure?.... Renal functions.
Investigations Urea creatinine and electrolytes CBC Testing for hep B and C Complement system ANA,Anti double stranded DNA antibodies. Imaging;U/S abdomen and chest. X ray chest. Genetic testing. Renal biopsy
INTERPRETATIONS Anemia , raised urea creatinine ,acidosis,hyperkalemia,hyperphosphatemia,indicate Chronic renal disease. Hyponatremia may be due to hyperlipidemia and due to water retention(pseudohyponatremia. Raised Hb and haemetocrat indicates haemodilution.reduced intravascular volume. Platelet is raised. Check liver enzymes..for Hepatitis B and C.and do screening for viruses.
MANAGEMENT OF NEPHROTIC SYNDROME A trial of corticosteroids is the first step in treatment of idiopathic nephrotic syndrome (INS) in which kidney biopsy is not initially indicated. patients aged 1-8 years with normal kidney function Normal kidney functions No macroscopic gross haemeturia No symptoms of systemic disease. Normal complement levels Negative viral screen No family hisory.
IMPORTANT DEFINITIONS RESPONSE; protein free urine on 3 consecutive days within 7 days. RELAPSE; protein +ve urine on 3 consecutive days within one week with edema. FREQUENT RELAPSING NS; steroid sensitive nephrotic syndrome with 2 or more relapses in 6 months or more than 3 in one year. STEROID DEPENDANT; responder who relapses while steroid is being tapered or within 14 days of stopping steroid treatment.
INITIAL NON RESONDER; no response during initial 8 weeks of therapy. LATE NON RESPONDER; an initial steroid responder who fails to respond to 4 week treatment in relapse.
SSNS steroid sensitive nephrotic syndrome Corticosteroids INDUCTION THERAPY Exclude active infections and other contraindications to steroids Oral prednisilone 60mg/m2/day…either single or divided doses for 4 weeks. 6 weeks therapy proves better . MAINTAINANCE THERAPY Oral prednisilone at 40mg/m2/day single morning dose at alternate Days for 4-6 weeks. Longer duration of maintenance therapy results in fewer relapses.
Relapse therapy For infrequent relapses steroid therapy may be resumed at 60mg/m2/day until proteinuria resolves.. Then switch to 40mg/m2/day for alternate days for 4 weeks. Other therapy Pneumococcal vaccines to all the patients. Diuretic therapy for symptomatic edema. with furosamide 2mg/kg/day. Anasarca with low intravascular volume ,albumin infusion, slow 1mg/kg/day can be considered.
HOME MONITORING Home monitoring of urine protein and fluid status is important. Parents should be trained to monitor first morning urine by dipstick. Record of daily weight,urine protein and steroid dose should be kept in log book. Any increase in urine protein or daily weight should be reported as early as possible.
DOSING AND REGIMENS Cyclophosphamide (2–2.5 mg/kg daily) is given orally for 8-12 weeks. Steroids are usually overlapped with initiation of CYP then tapered Patients must have weekly CBC counts to monitor for leukopenia. Patients must also maintain adequate hydration and take CYP in the morning (not at bedtime) to limit the risk of hemorrhagic cystitis
CYCLOSPORIN CSA can be used in those children who fail to respond to, or subsequently relapse after, treatment with CYP, or for children whose families object to use of CYP Initial doses of CSA are started at 5–6 mg/kg daily divided every 12 hours, adjusted for trough concentrations of 50–125 ng/mL Low-dose steroids are continued for a variable length of time
Kidney function and drug levels must be carefully monitored due to the risk of CSA induced nephrotoxicity.
Deterrence/Prevention Yearly influenza vaccination is recommended to prevent serious illness in the immunocompromised patient, as well as to prevent this possible trigger of relapse. Pneumococcal vaccination should be administered to all patients with INS to reduce the risk of pneumococcal infection. Vaccination should be repeated every 5 years while the patient continues to have relapses. Routine childhood vaccines with live virus strains are contraindicated in patients taking steroids and until off steroid treatment for a minimum of 1 month. Because of the high risk of varicella infection in the immunocompromised patient, in the nonimmune patient, post exposure prophylaxis with varicella-zoster immune globulin is recommended. Patient with varicella-zoster infection should be treated with acyclovir and carefully monitored Routine, nonlive viral vaccines should be administered according to their recommended schedules