Nephrotic Syndrome
DEFINITION:
- Nephrotic syndrome is a clinical complex characterized by a number of renal and extrarenal features, most prominent of which are
- Proteinuria (in practice > 3.0 to 3.5gm/24hrs),
- Hypoalbuminemia,
- Edema,
- Hypertension
- Hyperlipidemia,
- Lipiduria and
- Hypercoagulabilty(result of Loss of Antithrombin III)
PATHOPHYSIOLOGY:
- Proteinuria :The glomerular structural changes damage to the endothelial surface, the glomerular basement membrane, or the podocytes..
- Hypoalbunemia : It is due to both the proteinuria and due to the increase renal catabolism (in tubules).
- Metabolic consequences of proteinuria
- Infection
- Hyperlipidemia and atherosclerosis
- Hypocalcemia and bone abnormalities
- Hypercoagulability
- Hypovolemia
Infection in NS:
- Urinary immunoglobulin losses
- Edema fluid acting as a culture medium
- Protein deficiency
- Decreased bactericidal activity of the leukocytes
- Immunosuppressive therapy
- Urinary loss of a complement factor (properdin factor B) that opsonizes certain bacteria
Hyperlipedemia :
- Due to increase hepatic lipoprotein synthesis that is triggered by reduced oncotic .
- Defective lipid catabolism has also important role.
- LDL and cholesterol are increased in majority of patients whereas VLDL and triglyceride tends to rise in patients with severe disease.
- It increases the relative risk for MI 5.5 fold and coronary death 2.8 fold.
- Hypercoagulability :Multifactorial in origin
- Increase urinary loss of antithrombin III.
- Altered levels and/or activity of protein C & S.
- Hyperfibronogenemia due to increase hepatic synthesis.
- Impaired fibrinolysis due to decrease plasminogen.
- Increase platelet aggregability – relative immobility – haemoconcentragtion from hypovolemia. – hyperlipidemia
- Alteration in endothelial function
Hypocalcemia :
- low serum albumin level.
- Hypovolemia :Hypovolemia occurs when hypoalbuminemia decreases the plasma oncotic pressure, Resulting in a loss of plasma water into the interstitium and causing a decrease in circulating blood volume
ETIOLOGY:
Primary causes include-
- Minimal-change nephropathy(70-90% children and 10- 15%inadult)
- Focal glomerulosclerosis (15%inadult)
- Membranous nephropathy (30%inadult)
- Mesangial proliferative glomerulonephritis .
- Rapidly progressive glomerulonephritis
Secondary causes include
- Diabetes mellitus
- Lupus erythematosus
- P. malariae
- Amyloidosis and paraproteinemias
- Viral infections (eg, hepatitis B, hepatitis C, HIV )
- Preeclampsia
|
Gene |
Chromosome |
Protein |
Location |
Disease |
|
NPHS l |
19 13 q |
nephrin |
slipt diaphragm |
Nephrotic syndrome of finnish type |
|
NPHS2 |
125-31 (-1 |
podocin |
slit diaphragm |
Steroid resistant nephrotic syndrome |
SYMPTOMS & SIGNS:
- Anorexia,
- Malaise,
- Puffy eyelids,
- Retinal sheen,
- Abdominal pain,
- Wasting of muscles, and
- Edema:(due to Hypoalbuminemia) the edema is mobile – detected in the eyelids in the morning and in the ankles after ambulation
- Muehrcke lines in nails
Focal edema may be the reason for seeking help for such complaints as:
- Difficulty breathing (pleural effusion or laryngeal edema),
- Substernal chest pain (pericardial effusion),
- Scrotal swelling,
- Swollen knees (hydroarthrosis),
- Swollen abdomen (ascites), and
- Abdominal pain from edema of the mesentery.
- An early sign of NS is frothy urine.
- At presentation,proteinuria is usually > 2 gm/m2/day, or a urine protein/creatinine ratio is > 2
- Orthostatic hypotension and even shock may develop in children.
- Finnish of nephrotic syndrome is caused by defect in Nephrin protein
- Adults may be hypo-, normo-, or hypertensive.
- Oliguria and even Acute renal failure may develop because of hypovolemia and diminished perfusion.
- Prolonged NS may result in nutritional deficiencies, including
Protein malnutrition:
- Proteins increased in nephrotic syndrome Fibrinogen,Lipoproteins ( due to increased synthesis )
- Proteins decreased in nephrotic syndrome Albumin, Transferrin, Cholecalciferol binding protein,Thyroxin binding globulin
Myopathy,
- Decreased total Ca++, tetany
- Spontaneous peritonitis and opportunistic infections
- Coagulation disorders, with decreased fibrinolytic activity
- Episodic hypovolemia, are a serious thrombotic risk ( renal vein thrombosis).
- Hypertension with cardiac and cerebral complications
- Hyperlipidemia and hypercholesterolemia, secondary to increased hepatic synthesis of lipoproteins and decreased clearance of lipoproteins from the circulation.
- Hyperlipidemia in these patients also cause systemic atherosclerosis.
- Marked reduction of HDL receptor protein expression also contribute to increased atherosclerosis.
- All of these, acts as predisposing factors for the development of coronary artery disease.
DIAGNOSIS:
- Urinalysis
- Urine sediment examination
- Urinary protein measurement (24-hr)
- Serum albumin >2.5g/dl l
- Serologic studies for infection and immune abnormalities
- Renal ultrasonography
- Renal biopsy
MANAGEMENT:
Specific treatment
- In minimal-change nephropathy, glucocorticosteroids, such as prednisone, are used.
- Children who relapse may be treated with rituximab
- In some lupus nephritis, prednisone and cyclophosphamide are useful
- Secondary amyloidosis with nephrotic syndrome may respond to anti-inflammatory treatment of the primary disease.
- Oral cyclosporine for Steroid resistant nephrotic syndrome secondary to FSGS not responsive to methylprednisolone
Management Diet and activity
- The diet in patients with nephrotic syndrome should provide adequate energy (caloric) intake and adequate protein (1-2 g/kg/d).
Management Acute Nephrotic Syndrome in Adults
- Diuretics will be needed; furosemide, spironolactone, and even metolazone may be used. Volume depletion may occur with diuretic use, which should be monitored.
- Anticoagulation has been advocated by some for use in preventing thromboembolic complications,
Long-Term Monitoring- Follow-up care in patients with nephrotic syndrome includes
- Immunization,
- Treatment of relapses of steroid-responsive nephrotic syndromes,
- Monitoring for steroid toxicity, and
- Monitoring of diuretic and angiotensin antagonist regimens.
Medication Summary
- Corticosteroids (prednisone)
- Cyclophosphamide
- Cyclosporine
- Rituximab
- Mycophenolate
- Diuretics
- ACE inhibitors and
- ARB
Exam Question
- In nephrotic syndrome Transferrin, Albumin & Ceruloplasmin are reduced
- Oral cyclosporine for Steroid resistant nephrotic syndrome secondary to FSGS not responsive to methylprednisolone
- Edema in nephrotic syndrome is due to Hypoalbuminemia & Sodium and water retention
- Finnish of nephrotic syndrome is caused by defect in Nephrin protein
- The most common gene defect in idiopathic steroid resistant nephrotic syndrome NPHS 2
- Action of Tolbutamide, Diazepam & Valproate is reduced with nephrotic syndrome and hypoalbuminemia.
- Nephrotic syndrome increases the susceptibility to coronary artery disease
- Hypercoagulation in nephrotic syndrome is a result of Loss of Antithrombin III
- Muehrcke lines in nails are seen in nephrotic syndrome
- Nephrotic syndrome is the hall mark of Membranous Glomerulopathy,Minimal change disease & Focal segmental Glomerulosclerosis
- Basic abnormality in a case of nephrotic syndrome is proteinuria
- Membranoproliferative glomerulonephritis is common in both nephritic syndrome and nephrotic syndrome
- Patient with nephrotic syndrome on longstanding corticosteroid therapy may develop Hyperglycemia,Neuropsychiatric symptoms & Suppression of the pituitary adrenal axis
- Patient with congenital nephrotic syndrome requires renal biopsy
- Serum albumin level below 2.5g/dl l is seen in nephrotic syndrome in child
- Hyperglycemia ,Neuropsychiatric symptoms & Suppression of the pituitary adrenal axis are the side effects of long term steroid therapy in nephrotic syndrome
- Malaria causing nephrotic syndrome is P. malariae
- Most common cause of nephrotic syndrome in adult in Membranous glomerulonephritis
- Most common cause of nephrotic syndrome in children is Minimal change disease
- A child had hematuria and nephrotic syndrome (minimal change disease) shows Glomerular function is lost due to loss of poly charge on both sites of glomerular foot process
- Lipid cast are seen in Nephrotic syndrome
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