Nephrotic syndrome

• Definition

• Pathogenesis

• Classification

• Causes , most common ?

• Complicaions

• Treatment

• Follow up

• Definition :a type of kidney disease that results in proteinuria, peripheral edema, hyperlipidemia, and hypoalbuminemia .

• Criteria :

Protein –creatinine ratio more than 3.5 mg /mg or 24 h. urin collection of protein of more than 3.5 g/24 hours

Hyperlipidemia

Hypoalbuminemia

Pathogenesis • the glomerulus becomes permeable to large

molecules (e.g., albumin) • this loss of albumin (proteinuria) results

in hypoalbuminemia and edema

• associated with a hypercoagulable state • pathophysiology unclear but may be due to loss of

antithrombin and plasminogen proteins

• increased lipid synthesis secondary to proteinuria • this in turn results

in hypercholesterolemia and hyperlipidemia

Classification

• Primary glomerular disease • focal segmental glomerulosclerosis (THE MOST COMMON CAUSE OF PRIMARY

NEPHTOTIC SYDROME )

• membranous nephropathy

• minimal change disease

• Secondary causes • diabetic nephropathy ( THE MOST COMMON CAUSE OF BOTH NEPHROTIC

SYNDROME AND ESKD )

• systemic lupus erythematosus

• Amyloidosis……………..etc

Symptoms • Facial swelling is a common presenting feature in children and younger

adults , with periorbital oedema often being the first evidence that something is wrong; oedema may progress to involve the whole body.

• Adults tend to present with peripheral oedema affecting the ankles and legs, which may progress to involve the whole body.

• Some patients may notice frothiness of their urine.

• Hypercoagulability may manifest as venous or arterial thrombosis - eg, deep vein thrombosis, myocardial infarction.

• Recurrent infections and/or general fatigue, lethargy, poor appetite, weakness or episodic abdominal pain may cause presentation to a doctor.

Signs • Clinical signs of nephrotic syndrome include:

• Oedema (oedema of dependent parts or generalised oedema are the main clinical findings): periorbital oedema (facial oedema may be found in children), lower limb oedema, oedema of the genitals, ascites.

• Tiredness.

• Leukonychia.

• Breathlessness: pleural effusion (occasionally, severely hypoalbuminaemic cases may have pleural effusions or ascites), acute kidney injury.

• Breathlessness with chest pain: pulmonary embolism, myocardial infarction.

• Dyslipidaemia: eruptive xanthomata, xanthelasmata.

Investigations • Urine dipstick analysis: proteinuria and check for microscopic haematuria.

• Midstream urine for microscopy, culture and sensitivities to exclude urinary tract infection.

• Quantify proteinuria using an early morning urinary protein:creatinine ratio or albumin:creatinine ratio.

• Maltese cross in urin sediment

• FBC and coagulation screen.

• Renal function tests.

• LFTs (to exclude liver pathology); bone profile (calcium, phosphate, alkaline phosphatase).

• Check for other systemic diseases and causes of nephrotic syndrome: • ESR and CRP. • Fasting glucose. • Immunoglobulins, serum and urine electrophoresis. • Autoimmune screen if an underlying autoimmune disease is suspected: autoantibodies and complement

levels. • Hepatitis B and hepatitis C; HIV.

………….Continuation

• CXR and abdominal or renal ultrasound scan (especially if renal function is abnormal): to check for pleural effusion or ascites, the presence of two kidneys, the size and shape of the kidneys and for any urinary tract obstruction.

• Consider complications: • Lipids - hyperlipidaemia. • Doppler ultrasound of leg veins in suspected deep vein thrombosis. • Abdominal ultrasound, renal vein Doppler scan, venography of the inferior vena cava,

CT and MRI scanning of the abdomen if renal vein thrombosis is suspected. • Ventilation-perfusion scan - 'VQ' nuclear medicine lung scan; CT, pulmonary

angiography for pulmonary embolism.

• Renal biopsy under ultrasound; renal biopsy may be helpful to guide diagnosis and treatment but is not indicated in all patients with nephrotic syndrome.

Management principles • Diet and fluids:

• Reduce salt intake in the diet (avoid processed foods and adding salt to food). • Give a diet with adequate calorific intake and sufficient protein content (1-2 g/kg

daily). • Fluid restriction is not usually necessary (if severe enough to need this then the

patient may need admission).

• Hyperlipidaemia - does not initially require therapy but may do so if prolonged.

• Oedema: • Oedema is treated through diuretic therapy with furosemide (~1 mg/kg/day) • Check weight regularly to assess response to diuretics and ensure fluid retention is

not worsening, or that the patient is over-diuresed. • Patients with very low albumin levels may not respond to diuretics and may require

admission to receive intravenous albumin therapy.

• Other forms of nephrotic syndrome are less treatment-responsive; angiotensin-converting enzyme (ACE) inhibitors are frequently used in adults to some effect

• In pateints who do not respond to steroids, treatment may be with other immunomodulatory drugs such as cyclophosphamide, ciclosporin, tacrolimus .

Complications • Complications of nephrotic syndrome include:

• Decreased resistance to infections, due to urinary immunoglobulin loss.

• Increased risk of venous thromboembolism. Adults with membranous nephropathy are at particular risk.

• Acute kidney injury may rarely occur as a spontaneous complication of nephrotic syndrome. Acute kidney injury may also be caused by excessive diuresis, interstitial nephritis due to use of diuretics or NSAIDs, sepsis or renal vein thrombosis.

• Chronic kidney disease may occur as a result of an underlying cause - eg, amyloidosis or diabetes.

Steroid-resistant nephrotic syndrome is associated with a high risk of developing end-stage kidney disease.

• Increased risk of osteitis fibrosa cystica and osteomalacia due to loss of vitamin D-binding protein and its complexes in the urine, through a combination of calcium malabsorption and secondary hyperparathyroidism.

Referral and admission • Initial management should focus on investigating the cause, identifying complications

and managing the symptoms of the disease.

• Most patients do not require acute hospitalisation. All patients should be referred urgently to a nephrologist for further investigation. Indications for acute admission include:

1. Severe generalised oedema, particularly if pleural effusion/oedema is causing respiratory compromise.

2. Tense scrotal/labial oedema.

3. Complications of the nephrotic state (eg, sepsis, pneumonia, myocardial infarction, deep vein thrombosis).

4. Inability to comply independently with therapy or with the condition in the family.

5. Any features of a possible nephritic syndrome such as haematuria, hypertension and impaired renal function parameters.

FSGS • Some glomeruli ( focal ) , and part of the

glomerulus ( segmental )

• The leading cause of primary nephrotic syndrome , and the most common primary glomerular disease leading to ESRD in USA .

• More common in blacks and Hispanics

• Causes of FSGS :

Primary ,

Familial ,

Secondary to HIV ,

Sickle cell disease ,

Morbid obesity ,

Reflux nephropathy,

Heroin abuse .

Management

• ACE-I or ARBS to target a BP of less than 130/80 and control proteinuria ( to forstall progression of disease )

• For pateints with nephrotic range proteinuria or risk factors of progression to ESKD immunosuppressive medications must be used ; including corticosteroids , and calcineurin inhibitors , cyclophosphamide , mycophenolate mofitile , and Rituximab

Membranous glomerulonephritis

• The second leading cause of primary nephrotic syndrome ,

• Has a predilection to occur in adults older than 50 ys .

• Causes :

Primary ( insitu immune complex disease , meaning ?)

Secondary to :

SLE ,

Hepatitis B and C ,

Malaria

Malignancies ( solid tumors )

Medications ( e.g. NSAIDS )

• Membranous glomerulopathy has the HIGHEST prevalence of renal vein thrombosis compared with other cause of nephrotic syndrome .

Management

• Around 2/3 of pateints with membranous GN undergo spontaneous complete or partial remission ( hence no need for treatment ) ,

• The decision to treat is dependent on the clinical features and risk of disease progression

• Only Supportive treatment is required in most cases with treatment of hyperlipidemia , and hypercoagulable state , including it’s complications namely renal vein thrombosis .

• Screening for possible underlying solid tumors is also warranted in some cases .

• Follow up every 1-3 months of both proteinuria and GFR is required .

Minimal change disease

• The most common cause of nephrotic syndrome in pediatric age group .

• Pathology : light microscopy and immunofluorescence are normal , ( NIL DISEASE )

• Electron microscopy shows effacement of podocyte foot processes .

• Causes :

Idiopathic ,

Associated with atopic diseases , like ?

Lymphomas ,

Thymoma ,

Infectious mononeucleosis

Drugs like :Gold , penicillamine , rifampicine

………….etc .

Treatment

• Most pateints with MCG are responsive to daily or alternate day prednisolone , at 1 mg /kg/day or 2 mg /kg /eod , for 8-16 weeks , with complete remission achieved in 70 % of cases .

• Immunosuppresive therapy is used for

Secondary nephrotic syndrome

• Secondary to systemic diseases , most commonly diabetes ( diabetic nephropathy ) , amyloidosis , SLE , HIVAN, Hepatitis B , and multiple myeloma .

Amyloidosis

• How many types of amyloidosis do you know ?

• What are the causes ?

• How does it manifest ?

• Ho is it diagnosed ?

Treatment of secondary nephrotic syndrome

• Treatment of secondary nephrotic syndrome depends manly on treating the underlying systemic illness, including the following

• Adequate control of diabetes , with use of ACE-I or ARBS for control of both proteinuria and blood pressure

• Aggressive immunosuppressive therapy for lupus nephritis ( especially stage III and IV )

• Antiretroviral therapy for HIVAN

• Bone marrow transplantation for Amyloidosis ( supportive treatement with melfalane ) ……..etc .

Renal biopsy

• Nephrotic range proteinuria is one of the major indications for a renal biopsy

• Biopsies are absolutely contraindicated in the following situation:

• Uncontrolled bleeding diathesis

• Biopsies are relatively contraindicated when:

• Uncontrolled hypertension (>160/95)

• Uncooperative patient

• Patient unable to consent

• Solitary kidney. This is a 'big decision' and should be carefully made by a consultant and the patient

• Obstructed kidneys

• Small kidneys (less than 10 cm; less than 9 cm in a small patient)

• Anatomical abnormalities (eg vascular lesion)

• Renal neoplasm, multiple cysts, abscess or pyelonephritis

Thank you