nephrotic syndrome in chuldren diagnosis and management

nephrotic syndromee

1. Nephrotic syndrome diagnosis and management Presented by: Dr.Raja ’ Najajreh Supervised by :Dr Amani Salman

2. Outline : Brief review of definition and pathogenesis classification of nephrotic syndrome Clinical manifestations Diagnosis Management

3. Definition : Clinical presentation of glomerular diseases, associated with increase permeability across the filtration barrier , Characterized by heavy proteinuria (proteinuria > 50mg/kg/day , > 40m g/m2/ Hr ) With the triad of clinical findings : - hypoalbuminemia (≤2.5 g/ dL ) - edema - hyperlipidemia (cholesterol >200 mg/ dL ) ** Without treatment, nephrotic syndrome in children is associated with a high risk of death, most commonly from infections. Fortunately, 80 % of children with nephrotic syndrome respond to corticosteroid therapy 

4. Pathogenesis:

5. Classification and Etiology Primary / idiopathic NS: NS in absence of systemic disease . includes multiple histologic types: Minimal change disease :the most common membranous nephropathy focal segmental glomerulosclerosis : focal mesangial cell proliferation and segmental scarring on light microscopy membranoproliferative glomerulonephritis

6. Secondary NS: Nephrotic syndrome secondary to systemic diseases such as: systemic lupus erythematosus Henoch- Schönlein purpura malignancy (lymphoma and leukemia) infections (hepatitis, HIV, and malaria) Drugs : Captopril ,Penicillamine, Gold , NSAID ,Pamidronate , other bisphosphonates Interferon, Mercury, Heroin, Lithium, Rifampicin, Sulfasalazine

7. Congenital NS: Number of syndromes are caused by mutations in genes that encode critical protein components of the glomerular filtration apparatus. Congenital nephrotic syndrome is defined as nephrotic syndrome manifesting at birth or within the first 3 months of life mutations in four genes (NPHS1, NPHS2, WT1, and LAMB2), first three of which encode components of the glomerular filtration barrier Finnish type of congenital NS : caused by mutations in the NPHS1 or NPHS2 gene, which encodes component of slit diaphragm Denys- Drash syndrome: mutations in the WT1 gene, which results in abnormal podocyte function Pierson syndrome

8. Clinical Consequences of NS: Edema : most common presenting symptom. Start with periorbital swelling that decreases throughout the day. With time, the edema becomes generalized, with the development of ascites, pleural effusions, and genital edema. Anorexia, irritability, abdominal pain, and diarrhea are common Hyperlipidemia :increase in cholesterol, triglycerides, low-density lipoproteins, and very-low-density lipoproteins. The high-density lipoprotein level remains unchanged or is low Elevated blood pressure :common in patients with GN’s , infrequent with MCD Hematuria : microscopic hematuria seen in 20% of cases of Idiopathic NS Gross hematuria seen in patients with GN

9. Associated complications: - Increased Susceptibility to Infections due to immunologic impairment( hypoglobulinemia as a result of the urinary losses of immunoglobulin . In addition, defects in the complement cascade from urinary loss of complement factors - Thromboembolism due to hypercoagulability : vascular stasis from hemoconcentration , thrombocytosis and intravascular volume depletion. increase in hepatic production of fibrinogen along with urinary losses of antithrombotic factors such as antithrombin III and protein S.

10. Diagnosis: Although Edema is generally the presenting sign, the diagnosis is confirmed by presence of both: urinary protein excretion > 50mg/kg/day , 40 mg/m2/ hour hypoalbuminemia Clinical and laboratory findings are used to confirm the diagnosis of NS and are also used to diagnose specific underlying causes of nephrotic syndrome

11. Approach - Urinalysis First voiding to measure urinary protein/ creatinine ratio 24 hr urine collection Blood tests including : albumin , CBC, electrolytes , KFT and complements Other tests( if required) : - ANA (if features of SLE presents ) - HIV ,hepatitis B,C - Kidney biopsy

12. Urinalysis : urine dipstick measures protein concentration rather than the rate of protein excretion , so can’t be used to make the diagnosis of nephrotic syndrome. The urinary dipstick demonstrates a high albumin concentration (3+ to 4+, 300 to >1000 mg/ dL ). It’s used as a screening test while awaiting confirmation by quantitative protein excretion studies. Patients with idiopathic nephrotic syndrome have a relatively inactive urine sediment ( ie , oval fat bodies and hyaline casts, but few red cells and no red cell or other cellular casts). Hematuria :commonly seen in patient ‘s with GN

13. Urine protein excretion : Quantitative measurement of protein based upon timed 24hr urine collection ,of nephrotic range proteinuria Alternative method , protein / creatinine ratio on spot urine sample > 2 mg/mg

14. blood tests: - serum albumin :Hypoalbuminemia is one of the criteria that defines nephrotic syndrome. - Lipids : Hyperlipidemia is a characteristic feature of nephrotic syndrome. Serum total cholesterol, triglycerides, and total lipids are elevated .The increase in cholesterol is inversely correlated to the serum albumin concentration - Kidney function studies: is moderately impaired with elevation of serum creatinine in a minority of children with MCD primarily thought to be due to intravascular volume depletion - CBC: Hemoconcentration and thrombocytosis( as result of volume contraction ) may contribute to hypercoagulability and thrombotic complications

15. - Electrolytes : Hyponatremia can be present , due to decreased free water excretion form hypovolemic stimulation of the release of ADH Potassium may be high( in oliguric patients) Serum Ca is low ( due to hypoproteinemia ), ionized Ca normal

16. Initial therapy versus biopsy : > 90% of patients with MCD respond to steroid 90 % of children who respond to steroid will do within the 1 st 4 weeks, remaining 10% respond after additional 2-4 more weeks As result > steroid can be initiated in patients Who fulfill the criteria for clinical diagnosis Of MCD : 1.Age > 1 year, < 10 years 2.with none of the following : Hypertension gross hematuria, marked elevation in crea 3.Normal complement levels 4.No extra-renal symptoms

17. Management : Initial steroid therapy : Oral prednisone at a dose 60mg/m2/day or 2 mg/kg/day in 1 or 2 divided doses , for 4 weeks With continuous monitoring of urine protein levels ** Further therapeutic decisions including duration of therapy are based on response within the 1 st 4 weeks

18. Following initial treatment , the disease may take any of the following courses : Remission : disappearance of proteinuria ( trace or nil ) for 3 early morning specimen continue on same daily dose for 30 days, then switch to alternate day therapy. alternate day therapy Tapered over 1-2 months No remission within 1 st 4 weeks : 1-administer 3 IV pulses of methylprednisolone every other day, If persistent proteinuria1 week after that >> steroid resistant 2-continue on same daily dose steroid therapy for another 4 weeks , if fail to respond to maximum 8 weeks , considered steroid resistant 3- biopsy patients without additional steroid , and histologic findings guide further therapeutic decisions

19. Initial or infrequent relapse : + urine analysis for 3 early morning specimens ,after being in remission OR 3 or less relapses/year Administer daily prednisone until proteinuria disappeared for at least 3 days , alternate-day therapy is then begun and dose tapered to 15-20 mg/m2 every other day for another 4 weeks then discontinued Frequent relapses / steroid dependent :4 or more relapses/year or 2 or more relapses in the 6 months after diagnosis , 25-30 % of steroid responsive will developed FRNS .4 Steroid dependent is a relapse during steroid tapering or a relapse within 2 wk of the discontinuation of therapy cont. on same daily dose until remission , and alternate day therapy (15-20mg /m2) for 12-18 months

20. Managing clinical Sequelae of NS Edema : severe symptomatic edema, including large pleural effusions, ascites, or severe genital edema, should be hospitalized - Salt restriction - Water/fluid restriction - Administration of loop diuretics If patient has severe generalized edema with evidence of intravascular volume depletion (e.g., hemoconcentration , hypotension, tachycardia), administration of IV albumin (0.5-1.0 g albumin/kg)

21. infection control : prevention of infection by vaccination with pneumococcal and varicella vaccines if not previously immunized families should be counseled regarding the signs and symptoms of serious infections such as cellulitis, peritonitis, and bacteremia, to early identify and treat them Thromboembolism : Prevention by mobilization and avoidance of hypovolemia signs of thromboembolism should be evaluated by appropriate imaging studies to confirm the diagnosis Maintenance of adequate protein intake and Low fat diet

22. Steroid resistant nephrotic syndrome : Defined as failure to respond to initial steroid therapy Children with steroid-resistant nephrotic syndrome require further evaluation to determine the etiology including diagnostic renal biopsy , KFT, And screening for genetic disorders should be performed therapeutic decisions are based on underlying cause. Implications of SRNS : 50% risk of ESRD within 5 years if does not achieve partial or complete remission. poor quality of life, hypertension, serious infections, and thromboembolic events.

23. Alternative Therapies to Corticosteroids: Steroid-dependent patients, frequent relapsers , and steroid-resistant patients are candidates for alternative therapies ** particularly if they have severe corticosteroid toxicity ( cushinoid appearance, hypertension, cataracts, and/or growth failure). Cyclophosphamide: in patients with frequently relapsing and steroid-dependent nephrotic syndrome (2mg/kg ) is given as a single oral dose for a total duration of 8-12 wk. Alternate-day prednisone therapy is often continued during cyclophosphamide administration. cyclosporine or tacrolimus: are recommended as initial therapy for children with steroid-resistant nephrotic syndrome

24. Thank you