NEPHROTIC SYNDROME Ayça Vitrinel, MD

Nephrotic syndrome (NS) NS is characterized by Proteinuria 40 mg/m2/hr in children 3.5 gr/24 hr in adults Hypoalbuminemia <2.5 gr/dl Edema Hyperlipidemia

Etiology Idiopathic NS (90%) Membranous nephropathy Minimal change (85%) Mesangial proliferation (5%) Focal sclerosis (10%) Membranous nephropathy Membranoproliferative GN (10%)

The nephrotic syndrome consists of proteinuria, hypoalbuminemia, edema, hyperlipidemia. Of these, the proteinuria is primary, with the development of hypoalbuminemia, edema, and hyperlipidemia as secondary findings.

Pathophysiology(1) Proteinuria Increase in glomerular capillary wall permeability The mechanism of this increase is unknown T cell dysfunction leads to alteration of cytokines Loss of negatively charged glycoproteins within the capillary wall Focal segmental glomerulosclerosis is characterized by a plasma factor Perhaps produced by lymphocytes Increases glomerular permeability to proteins

Pathophysiology(2) Edema Appears when the serum albumin level falls below 2.5 g/dl Inıtıated by the development of hypoalbuminemia (result of urinary protein loss) Decrease in the plasma oncotic pressure Permits transudation of fluid from the intravascular compartment to the interstitial space The reduction of intravascular volume Decreases renal perfusion pressure Activating renin-Agt-aldosteron system Stimulates distal tubular reabsorbtion of Na

Pathophysiology(3) The reduced intravascular volume stimulates the release of ADH Enhances the reabsorbtion of water in the collecting duct The reabsorbed Na and water are lost into the interstitial space exacerbating the edema

Pathophysiology(4) Hyperlipidemia Cholesterol, triglycerides and lipoprotein levels are elevated Hypoproteinemia stimulates generalized protein synthesis in the liver, including the lipoproteins Lipid catabolism is diminished owing to reduced plasma levels of lipoprotein lipase, the major enzyme system that removes lipids from the plasma

Idiopathic Nephrotic syndrome Minimal change disease Mesangial proliferation Focal segmental glomerulosclerosis The cause remains unknown The disease is mediated by immunologic mechanisms-abnormal T-lymphocyte function

Pathology (1) Occurs in three morphologic patterns Minimal change disease The glomeruli appear normal or show a minimal increase in mesangial cells and matrix Electron microscopy reveals retraction of the epithelial cell foot processes More than 95% of children respond to corticosteroid therapy

Pathology (2) Mesangial proliferative group Focal sclerosis Diffuse increase in mesangial cells and matrix 50-60% patients respond to CST therapy Focal sclerosis The majority of glomeruli appear normal or show mesangial proliferation, others show segmental scarring in one or more lobules Frequently progressive Lead to end-stage renal failure May recur in a transplanted kidney

Clinical manifestations (1) More common in boys than girls (2:1) Most commonly appears between the ages of 2-6 years May follow an apparent viral URTI, reactions to insect bites, bee stings or poison ivy

Clinical manifestations (2) Edema around the eyes and in the lower extremities Edema becomes generalized Weight gain, development of ascites or pleural effusions, declining urine output Anorexia, abdominal pain, diarrhea, hypertension is common

Diagnosis (1) Urinalysis reveals +3 or +4 proteinuria Microscopic hematuria may be present (20%) Spot urine protein/creatinine ratio exceeds 2.0 Renal function may be normal or reduced Serum cholesterol or triglyceride levels are elevated

Diagnosis (2) Serum albumin level is generally less than 2 g/dl Total serum calcium level is diminished C3 level is normal Children with onset of NS between the ages of 1 and 8 years are likely to have steroid responsive minimal change disease no biopsy is indicated

Complications(1) Infections Decreased Ig levels Edema fluid acting as a culture medium Protein deficiency Decreased bactericidal activity of leukocytes Immunosuppressive therapy Decreased perfusion of spleen due to hypovolemia Loss in the urine of a complement factor that opsonizes certain bacteria

Complications(2) Infections S.pneumoniae is the most common organism Peritonitis Sepsis Pneumonia Cellulitis Urinary tract infection S.pneumoniae is the most common organism E.coli may be encountered

Complications(3) Arterial and venous thrombosis Increased prothrombotic factors Fibrinogen, thrombocytosis, hemoconcentration, relative immobilization Decreased fibrinolytic factors Urinary losses of ATIII, protein C and S

Treatment Edema Na intake reduced Steroids

Prognosis Most children with steroid responsive nephrosis have repeated relapses until the disease resolves spontaneously toward the end of the 2nd decade

Secondary NS(1) Glomerulonephritis NS may develop during the course of any type of GN but is most common in association with: Membranous age>8 Membranoproliferative hypertension Poststreptococcal hematuria LE renal dysfunction Malaria extrarenal symptoms HSS

Secondary NS(2) Tumors NS may be associated with several extrarenal neoplasms Carsinomas, lymphomas Tm produces a lymphokine that increases glomerular capillary wall permeability

Secondary NS(3) Drugs Penicilamine probenecid phenytoin Captopril ethosuximid gold Metimazole NSAID lithium Mercury comp. procainamide chlorpropamide

Secondary NS(4) Infections Hepatitis B Hepatitis C Leprosy HIV

Congenital NS Infants develop NS within the first 3 months of life Finnish type (autosomal recessive) Gene has been located to the long arm of chromosome 19 Antenatal diagnosis is possible