Nephrotic Syndrome PDF

Proteinuria and nephrotic syndrom Dr.farhad salih dosky Protienuria Definition and types Diagnostic tests Causes Evaluation managment Definition and types Is define as presence of protein in the urine. Could be Physiological (fever , exercise ,stress , seizure) it...

Proteinuria and nephrotic syndrom Dr.farhad salih dosky Protienuria Definition and types Diagnostic tests Causes Evaluation managment Definition and types Is define as presence of protein in the urine. Could be Physiological (fever , exercise ,stress , seizure) it doesn't reflect renal disease Orthostatic is an exaggerated form of physiologic proteinuria. Pathological (glomerular or tubular). protienuria Spot urine protein 24 hours urine \creatinine ratio mg\mg protein excretion mg\m2\hr Pysiologic 40 mg \m2\hr or >1g \m2\24hr) Hypoalbuminemia Generalized edema Hyperlipdemia is almost always present. Hematuria (mostly microscopic ), hypertension, rasied urea levels occasionally observed.  Important terms Idiopathic NS:- is primary NS where the disease mechanism is not clear. Secondary NS:- NS secondary to systemic disease (SLE, HSP, hepatitis B). Urinary remission :- urinary albumin nil or trace for 3 consecutive days. Relapse :- heavy proteinuria for 3 consecutive days, was in remission previously. Frequent relapse:- two or more relapse \6 months or more than 3 relapse \1 year. Steroid dependence NS:-relapse during alternate day of prednisolone therapy or with in 14 days of discontinuation. Steroid resistant NS:-persistent proteinuria despite of high dose prednisolone for 8 weeks in the absence of infection or non adherence to medication. Congenital NS:- is NS in the 1st 3 months of the life. Pathogenesis of NS Pathogenesis of nephrotic syndrome Genetic abnormalities Immune dysfunction Circulating factors Podocyte and anti-proteinuric agents. Clinical features Onset of MCNS is usually between 2-6 years. More common in boys (60-70%). The child looks well. When start in 12-16 years ,the chance of presence of underlying lesions are higher. Onset is insidious with swelling around the eyes and facial puffiness noticeable at mornings but resolve when the child is up. In some cases URTI may be present. The facial puffiness may be ascribed to allergy, mumps, dental infection. May be associated with diarrhea. The swelling increases to involve the extremities abdomen and may become massive.  Evaluation The child should be examined to detect associated infection Features of systemic disorder(fever, rash, joint pain and swelling, organomegally, lymphadenopathy). In MCNS Blood pressure is normal but occasionally in patients with massive edema might be elevated. With remission blood pressure return to normal.  Urine analysis Urine examination shows 3-4+ protein by dipstick test. Urinary protein \creatinine ratio might be examined. The measurement of 24-hr urinary protein is not essential. Presence of microscopic hematuria suggests the likelihood of an underlying renal histologic lesion.  Blood examination Blood is examined for levels of urea, creatinine, electrolytes, proteins, and cholesterol. Serum albumin 250mg\dl. Sever anasarca is usually associated with serum albumin 500mg\dl. Dilutional hyponatremia C3 level is normal in MCNS. Ultrasound of abdomen and CXR. Monteux test. Renal biopsy is not done in a patients likely to have MCNS  Indications of renal biopsy in NS 1) Age 12 years at presentation, 2) Steroid resistance NS 3) Low C3 and or C4 level. 4) Sustain hypertension 5) Elevated serum creatinine 6) Features of systemic disease 7) Presence of gross or persistent microscopic hematuria.  Histological lesions of primary NS 1. MCNS ………most common 2. FSGS 3. MPGN 4. MN 5. others  Treatment of initial episode Prednisolone of the steroid of choice. 2mg\kg\day or (60mg\m2\day) in 2-3 divided dose for 6 weeks. 1.5 mg\kg (40 mg\m2) given in alternate days as single morning dose for more 6 weeks ,after which it is discontinued. During glucocorticoid therapy, the salt intake and food rich in fat should be restricted, Blood pressure should be monitored Counseling of the family about treatment compliance and steroid side effects.  Subsequent course Majority of the patients with MCNS suffer from relapses, which might precipitated by URTI. Patients categorized as infrequent relapses, frequent relapses and steroid dependent. Relapse treated with prednisolone until proteinuria resolve, and then on alternate days for 4 weeks. Repeated steroid therapy for frequent relapses may lead to unacceptable side effects. Treatment of frequent relapses and steroid dependence Patients with FRNS or SDNS requiring frequent course of prednisolone often develop serious steroid toxicity. Important side effects include cushioned features (obesity, hirshutism, striae), hypertension, impaired glucose tolerance test, cataract, growth retardation. Initially alternate long-term prednisolone therapy may be used. Steroid sparing agents 1. Levomisole (anti helminthic agent) 2. Cyclophosphmide (alkylating agent) 3. Mycofenolate mofetil 4. Cyclosporine /tacrolimus (calcineurin inhibitors). 5. Rituximab (monoclonal antibody)  Steroid resistance NS 3-6 doses of pales methyl prednisolone 20-30mg IV cyclophosphamide therapy 500-750 mg\m2 monthly for 6 months Calcineurin inhibitor for 2-3 years Retuximab 375mg\m2 General care Dietary management Control of edema Prevention and treatment of infection Psychological support Counseling of family regarding nature of disease, side effects of medication, how to test the protein in the urine. Nontraditional and hazardous medications should be avoided.  Complications of NS 1. Infections 2. Hypovolemia and acute kidney injury 3. Thromboembolism 4. Hyperlipidemia 5. Urinary loss of low molecular weight protein. 6. Hypoproteinemia and malnutrition 7. Flare up of T.B while on immunosuppressive therapy.  1-infection Children with NS specially if receiving immune suppressive therapy are susceptible to bacterial infections Such infections are considerable causes of morbidity and mortality Most common infections are peritonitis and cellulites. Empyema, bone and joint infections, sepsis, and tuberculosis are frequent. The chief pathogen is streptococcus pneumonia, and staphylococcal infection.  Causes of infection in NS Uses of steroids and immunosuppressant. Edema is good nidus for bacteria and causing spontaneous skin break Urinary loss of immunoglobulin Urinary loss of factor B Urinary loss of transferrin.  Peritonitis Mostly seen in patients with relapse and ascites. The onset is acute although with subtle and non specific features, including abdominal pain fever and vomiting. Diagnosis is made by examination of ascetic fluid which may be hazy or turbid. The presence of neutrophils (75-100/mm3) is confirmatory. Culture show s.peumoniae or gram negative bacilli (E.coli, hemophilus) Parenteral antibiotics with 3rd generation cephalosporin for 7-10 days is preferred.  Stress dose corticosteroids Suppression of hypothalamopitutary axis is common in patients who have received prednisolone(>1mg/kg/day) for more than 2 weeks in the preceding 6-12 months. During infection or stress or undergoing surgery, hydrocortisone is given 30-100mg/m2 /day in divided doses and then tepered by 50 present daily.  Outcome of NS In steroid sensitive NS prognosis is excellent. Most patients stop getting relapses between 14-20 years or even earlier, and recover without residual renal dysfunction. In steroid resistant NS patient at risk for progressive kidney disease. Thank you