Presentation on theme: "Nephrotic Syndrome..…(NS)"— Presentation transcript:
1 Nephrotic Syndrome..…(NS) Prepared by:-Mohammad Ali Al-shehri…..Supervised by :Dr..
2 Introduction Definition of NS Etiology of NS Pathology of NS Pathophysiology of NSClinical Manifestation of NSComplication NSLaboratory DataDiagnosisTreatment
3 Nephrotic syndromeNephrotic syndrome (NS) results from increased permeability of Glomeulrar basement membrane (GBM) to plasma protein. It is clinical and laboratory syndrome characterized by massive proteinuria, which lead to hypoproteinemia ( hypo-albuminemia), hyperlipidemia and pitting edema. (4-increase, 1-decrease).
4 Nephrotic Criteria:- *Massive proteinuria: qualitative proteinuria: or 4+,quantitative proteinuria : more than 40 mg/m2/hr in children (selective).*Hypo-proteinemia :total plasma proteins < 5.5g/dl and serum albumin : < 2.5g/dl.*Hyperlipidemia:serum cholesterol : > 5.7mmol/L*Edema: pitting edema in different degree
5 Nephritic Criteria -Hematuria: RBC in urine (gross hematuria) -Hypertension:≥130/90 mmHg in school-age children≥120/80 mmHg in preschool-age children≥110/70 mmHg in infant and toddler’s children-Azotemia（renal insufficiency）:Increased level of serum BUN 、Cr-Hypo-complementemia:Decreased level of serum c3
6 Classification: A-Primary Idiopathic NS (INS): majority The cause is still unclear up to now. Recent 10 years ,increasing evidence has suggested that INS may result from a primary disorder of T– cell function.Accounting for 90% of NS in child. mainly discussed.B-Secondary NS:NS resulted from systemic diseases, such as anaphylactoid purpura , systemic lupus erythematosus, HBV infection.C-Congenital NS: rare*1st 3monthe of life ,only treatment renal transplantation
8 Idiopathic NS (INS): Pathology:- Minimal Change Nephropathy (MCN): <80%The glomeruli appear normal basically Under Light microscopy, and Under Immunofluorescence*under Electron microscopy – fusion of the foot processes of the podocytes(2) Non—MCN： ＜20%*Mesangial proliferative glomerulonephritis(MsPGN): about 10%*Focal segmental glomerulosclerosis (FSGS): 5%*Membranous Nephropathy (MN) : 2%*Membrane proliferative glomerulonephritis(MPGN) : 1%*Others： rare,Cresent glomerulonephritis
9 NB:-*Nephrotic syndrome is 15 times more common in children than in adults.*Most cases of primary nephrotic syndrome are in children and are due to minimal-change disease. The age at onset varies with the type of nephrotic syndrome.
10 Pathophysiology:The Main Trigger Of primary Nephrotic Syndrome and Fundamental and highly important change of pathophysiology :- Proteinuria
11 Pathogenesis of Proteinuria:- Increase glomerular permeability for proteins due to loss of negative charged glycoproteinDegree of protineuria:-Mild less than 0.5g/m2/dayModerate 0.5 – 2g/m2/daySever more than 2g/m2/dayType of proteinuria:-A-Selective proteinuria: where proteins of low molecular weight .such as albumin, are excreted more readily than protein of HMWB-Non selective :LMW+HMW are lost in urine
12 pathogenesis of hypoalbuminemia *Due to hyperproteinuria----- Loss of plasma protein in urine mainly the albumin. *Increased catabolism of protein during acute phase.
13 pathogenesis of hyperlipidemia:- *Response to Hypoalbuminemia → reflex to liver --→ synthesis of generalize protein ( including lipoprotein ) and lipid in the liver ,the lipoprotein high molecular weight no loss in urine → hyperlipidemia*Diminished catabolism of lipoprotein
14 pathogenesis of edema:- *Reduction plasma colloid osmotic pressure↓ secondary to hypoalbuminemia Edema and hypovolemia*Intravascular volume↓ antidiuretic hormone (ADH ) and aldosterone(ALD) water and sodium retention Edema*Intravascular volume↓ glomerular filtration rate(GFR)↓ water and sodium retention Edema
15 How many pathological types causes nephrotic syndrome?
16 Clinical Manifestation:- IN MCNS , The male preponderance of 2:1: 1.Main manifestations:Edema (varying degrees) is the common symptomLocal edema: edema in face , around eyes( Periorbital swelling) , in lower extremities.Generalized edema (anasarca), edema in penis and scrotum.2-Non-specific symptoms:Fatigue and lethargyloss of appetite, nausea and vomiting ,abdominal pain , diarrheabody weight increase, urine output decreasepleural effusion (respiratory distress)
19 Investigations:- 1-Urine analysis:- A-Proteinuria : 3-4 + SELECTIVE. b-24 urine collection for protein>40mg/m2/hr for childrenc- volume: oliguria (during stage of edema formation)d-Microscopically:-microscopic hematuria 20%, large number of hyaline cast
20 Investigations:- 2-Blood: A-serum protein: decrease >5.5gm/dL , Albumin levels are low (＜2.5gm/dL).B-Serum cholesterol and triglycerides: Cholesterol ＞5.7mmol/L (220mg/dl).C-- ESR↑＞100mm/hr during activity phase.3.Serum complemen: Vary with clinical type. 4.Renal function
21 Kidney Biopsy:- Considered in: 1-Secondary N.S 2-Frequent relapsing N.S3-Steroid resistant N.S4- Hematuria5-Hypertension6- Low GFR
22 Differential Diagnosis of NS: D.D of generalized edema:-1-Protein –losing enteropathy2-Hepatic Failure.3-HF4-Protein energy malnutrition5-Acute and chronic GN6-urticaria? Angio edema
23 Complications of NS:-1-Infections:Infections is a major complication in children with NS. It frequently trigger relapses.Nephrotic pt are liable to infection because :A-loss of immunoglobins in urine.B-the edema fluid act as a culture medium.C-use immunosuppressive agents. D- malnutritionThe common infection : URI, peritonitis, cellulitis and UTI may be seen.Organisms: encapsulated (Pneumococci, H.influenzae), Gram negative (e.g E.coli
24 Vaccines in NS;- Complication … polyvalent pneumococcal vaccine (if not previously immunized) when the child is in remission and off daily prednisone therapy.Children with a negative varicella titer should be given varicella vaccine.
25 Complication….. 2-Hypercoagulability (Thrombosis). Hypercoagulability of the blood leading to venous or arterial thrombosis:Hypercoagulability in Nephrotic syndrome caused by:1-Higher concentration of I,II, V,VII,VIII,X and fibrinogen2- Lower level of anticoagulant substance: antithrombin III3-decrease fibrinolysis.4-Higher blood viscosity5- Increased platelet aggregation6- Overaggressive diuresis
26 3-ARF: pre-renal and renal 4- cardiovascular disease :-Hyperlipidemia, may be a risk factor for cardiovascular disease.5-Hypovolemic shock6-Others: growth retardation, malnutrition,adrenal cortical insufficiency
27 Management of NS:General (non-specific )*Corticosteroid therapy
28 General therapy:-Hospitalization:- for initial work-up and evaluation of treatment.Activity: usually no restriction , exceptmassive edema,heavy hypertension and infection.Diet Hypertension and edema: Low salt diet (<2gNa/ day) only during period of edema or salt-free diet. Severe edema: Restricting fluid intakeAvoiding infection: very important.Diuresis: Hydrochlorothiazide (HCT) ：2mg/kg.dAntisterone ： 2～4mg/kg.dDextran ： 10～15ml/kg , after 30～60m,followed by Furosemide (Lasix) at 2mg/kg .
29 Induction use of albumin:- Albumin + Lasix (20 % salt poor)1-Severe edema2-Ascites3-Pleural effusion4-Genital edema5-Low serum albumin
30 Corticosteroid—prednisone therapy:- Prednisone tablets at a dose of 60 mg/m2/day (maximum daily dose, 80 mg divided into 2-3 doses) for at least 4 consecutive weeks. After complete absence of proteinuria, prednisone dose should be tapered to 40 mg/m2/day given every other day as a single morning dose. The alternate-day dose is then slowly tapered and discontinued over the next 2-3 mo.
31 Treatment of relapse in NS: Many children with nephrotic syndrome will experience at least 1 relapse (3-4+proteinuria plus edema). daily divided-dose prednisone at the doses noted earlier (where he has the relapse) until the child enters remission (urine trace or negative for protein for 3 consecutive days). The pred-nisone dose is then changed to alternate-day dosing and tapered over 1-2 mo.
32 According to response to prednisone therapy: *Remission: no edema, urine is protein free for 5 consecutive days.* Relapse: edema, or first morning urine sample contains > 2 + protein for 7 consecutive days.*Frequent relapsing: > 2 relapses within 6 months (> 4/year).*Steroid resistant: failure to achieve remission with prednisolone given daily for 28 days.
33 Side Effects With Long Term Use of Steroids “Steroid toxicity hyperglycemiamyopathypeptic ulcerpoor healing of wound.HirsutismThromboembolism-Stunted growthCataracts- Pseudotumor cerebri-Psycosis-Osteoporosis- Cushingoid features-Adrenal gland suppression
34 Alternative agent:- When can be used: Cyclophosphamide Pulse steroids Steroid-dependent patients, frequent relapsers, and steroid-resistant patients.Cyclophosphamide Pulse steroidsCyclosporin ATacrolimusMicrophenolate