This lecture was conducted during the Nephrology Unit Grand Ground by a

Sub-intern under Nephrology Division,

Department of Medicine in King Saud University.

Nephrology Division is NOT responsible for the content of the presentation for it is

intended for learning and /or education purpose

only.

Nephrotic syndrome

Done by : Nora AlMahmoud

Objectives:

0Definition0Pathophysiology0Causes0Clinical manifestations 0Complication 0Diagnosis0Treatment

Definition

Clinical complex that include the following :1)Massive proteinuria (3.5g or more in adult).2)Hypoalbuminemia (<3mg/dl)3)Generalized edema4)Hyperlipidemia and lipidurea

0 Urinary loss of anticoagulants proteins, i.e.: protein C , protein S , and antithrombin

Hypercoagulable state

0Urinary loss of transport proteins

Iron , Copper , and Zinc deficiency

Pathophysiology Damage to Podocytes (glomerulus epithelial cells)

allows proteins to pass through a 'leaky' glomerulus into the urine.

Normally molecules of <20kDa will pass into the urine In Nephrotic syndrome molecules of >100kDa can

pass into the urine

Causes

0Causes of nephrotic syndrome vary according to age .

0In children : always caused by lesion primary to the kidney .

0In adult often due to renal manifestation of a systemic disease .

Primary causes

0Membranous GN0Minimal change disease 0Focal segmental glumerulosclerosis0Membranoproliferative GN

Membranous GN

0Most common cause in Adult0The 1ry disease is idiopathic 0The 2ry form is due to: -infection (Hepatitis C and B viruses , Malaria, syphilis ) - Drugs (gold, Captopril , penicillamine) - Neoplasm or Lupus 0Deposition of Ag-Ab complexes

Minimal change disease

0Most common cause in Children0Associated with Hodgkin’s and non-Hodgkin’s

lymphoma0No histological abnormality in light microscopy ,

Fusion of foot processes on Electron microscopy.

FSGN0Account for 25% of cases of nephrotic syndrome in adult

0Associated with: HIV , Heroin , sickle cell and obesity. 0 It has fair to poor prognosis – resistant to steroid therapy

– patient develop renal insufficiency within 5-10 years of diagnosis , the course is progressive.

Membranoproliferative GN

0Can be idiopathic or 2ry to chronic immune disease (Hepatitis C , Alpha1 antitrypsin , HIV , Malignancy )

0GBM alteration , sub endothelial leukocytes infiltration , predominant masengial involvement .

Secondary causes

0Systemic lupus erythematosus (SLE).0Amyloidosis.0Diabetes Mellitus.0Allergy.0 Infections.(HBV, HCV, HIV, Malria, syphilis).0Drugs(Gold)

Clinical Pictureedema first presents periorbitally Ankle edema Severe proteinuria increase BPMore severe features occur late or if untreated and may

include pulmonary effusion, genital edema and anasarca (severe generalised edema).

Complications

1. Venous thromboembolism 2. Extreme hypercholesterolaemia (>10mmol/L) 3. Infection 4. Renal Failure 5. Malnutrition

How to approach pt. with Neprotic syndrome?

0 Patient history - Identify medication or toxin exposure; risk factors for HIV or viral hepatitis; and symptoms suggesting other causes of edemaObtain history of diabetes, systemic lupus erythematosus, or other systemic illness0 Urine dipstick : Confirm proteinuria0 Random urine protein/creatinine ratio : Quantify degree of

proteinuria (ratio greater than 3 to 3.5)0 Serum creatinine : Rule out acute renal failure, assess glomerular

filtration rate0 Serum albumin : Assess degree of hypoalbuminemia0 Lipid panel0 Assess degree of hyperlipidemia

0 Additional studies suggested by patient factors: -HIV screening test - Identify HIV -Hepatitis serology panel -Identify hepatitis B or C -Serum or urine protein electrophoresis -Suggests amyloidosis or multiple myeloma -Rapid plasma reagin -Identify syphilis - Antinuclear antibodies or complement (C3 and C4) level -Identify systemic lupus erythematosus; complement levels may also be reduced in membranoproliferative disease

Diagnosis

0Urin analysis shows >3.5 g/24h : - Most often used: single spot urine for albumin and creatinine.0Most accurate test to determine etiology is : Renal Biopsy

Treatment3 Aims:

1) Treat fluid retention: Restrict salt and water intake loop diuretic +/- thiazide diuretic ACE inhibitor +/- Angiotensin 2 receptor antagonist

2) Avoid complications: prophylactic heparin prompt treatment of infection treat hyperlipidaemia (statins) target BP 125/75

3) Treat the underlying cause 0 steroids in all idiopathic 1ry renal disease0If steroids ineffective : -add Cyclophosphamide or Mycophenolate

0 ACE inhibitor used in all patients but does not reverse the disease

Nephrotic Vs. Nephritic syndromes

Nephrotic s. Nephritic s.

Pathogenesis Abnormal glomerular permeability due to number of conditions

Inflammation of the Glomeruli due to any of the causes of Glumerulonephritis

Causes 1ry and 2ry causes Poststrept. Glomerulonephritis is the most common cause

Lab finding Proteinuria >3.5g/24hHypoalbuminemia Hyperlipidemia , Fatty cast in the urine

HematuriaARF-Azotemia , OliguriaProteinuria if present mild

Clinical finding

Generalized EdemaHypercoagulable state Increase risk of infection

HTNEdema