Pathology of nephrotic syndrome
The primary corticosteroid-sensitive primary nephrotic syndrome usually does not include hypertension, renal failure and haematuria
The term "nephrotic nephrology" was first used by Friedrich Müller in 1906 to refer to kidney diseases whose anatomical lesions are only degenerative, without inflammatory properties. In 1908 Munk used the term "Fatty Kidney Failure" to refer to a type of kidney disease that clinically has oedema and proteinuria, anatomical disease with birefringent fat penetration in the kidney tubules and normal glomeruli.
Today, thanks to the advancement of kidney biopsy technology and electron microscopy, it is found that biochemical changes of fatty nephrotic occur in many different diseases, glomerular damage is also varied although the clinical and biochemical manifestations are relatively similar. Thus, fatty kidney failure is not a simple disease as previously thought.
Nephrotic syndrome (HCTH) usually presents with minimal glomerular damage or thickening and degenerative basal membrane damage of glomerular capillaries.
Primary corticosteroid-sensitive primary nephrotic syndrome usually does not include hypertension, renal failure and haematuria. In a large number of cases, there are no complications in adulthood.
The disease mainly occurs in children, 90% of cases occur at the age of 16 years. Frequency of 2 / 30,000 in children, in adults, it is less than 2 / 300,000.
In children, the primary nephrotic syndrome occurs in boys more than girls (male / female ratio is 2/1). The most common age in children is 2 to 8 years old, and is usually pure nephrotic syndrome.
Less common in adults, nephrotic syndrome is usually nephrotic and occurs in both sexes.
According to William G. Couser about 1/3 of adult patients and 10% of child patients have nephrotic syndrome as a symptom of a whole disease, usually Diabetes, Scorched lupus erythematosus or Amylose kidney. The remainder is primary nephrotic syndrome.
Fatty Kidney Failure: Minimal damage to loss of glomerular basal epithelial protrusion leg
HCTH due to glomerulonephritis (VCT):
Degenerative glomerulonephritis each drive, segment.
Diffuse proliferative glomerulonephritis.
Extra-vessel proliferative glomerulonephritis (sickle-shaped proliferation of VCT).
Secondary after the diseases
Systemic lupus erythematosus.
Inflammation around the nodular artery.
Salts of heavy metals Hg, Au ..
Medicine: Trimethadione, Paramethadione, Penicillamine, Probenecid.
Causes of blood vessels
Clogging of the aorta.
Renal venous obstruction.
Bacteria: streptococcus, syphilis, subacute endocarditis.
Parasites: malaria, Bilharziose.
Family and congenital HCTH.
Proteinuria in nephrotic syndrome is very much, usually over 3.5g / 24 hours / 1.73 m2 of body area, can reach 40g / 24 hours. In children, it has recently been proposed that the urinary protein needed for diagnosis is 1.66 g / day / m2 of body area, if the blood albumin falls below 25 g / l. Proteinuria changes depending on the glomerular filtration rate and blood albumin, so proteinuria can be reduced in the case of a large decrease in glomerular filtration rate or a very clear and rapid decrease of blood albumin.
Proteinuria may consist mainly of albumin or proteins with a smaller molecular weight: selective proteinuria. In other cases, proteinuria consists mostly of plasma proteins, especially IgG: called non-selective.
Proteinuria is caused by abnormalities of the glomerular barrier where selective permeability with macromolecules becomes abnormal.
In some cases, the very charge-selective barrier of macromolecules is disturbed: There are biochemical changes that are pervasive throughout the glomerular structure, this abnormality cannot be determined by microscopy. optical. Selective proteinuria is common in this situation.
In other cases, the barrier itself selects according to the size of the damaged macromolecules. There are abnormalities of the glomerular structure, conspicuous by optical microscopy. Proteinuria in this case is usually not selective.
Reduced blood albumin
Reduced blood albumin <30 g / l, more common is <20 g / l.
Hypoalbuminemia is mainly due to loss of albumin in the urine, a correlation between the level of proteinuria and blood albumin.
There is also an increase in the catabolism of the kidney to albumin: Albumin, after filtration, is reabsorbed in the proximal tubule by intracellular absorption and then degraded in the lysosomes.
There are two main mechanisms to compensate for the urinary loss of albumin
Increased hepatic albumin synthesis:
Normally, liver synthesizes 12-14 g albumin / day in adults, nephrotic syndrome can increase synthesis by about 20%. Thus, it can be seen that this synthesis is not sufficient to compensate for the loss of protein in the urine.
Factors such as age, poor nutrition, and pre-existing liver diseases may also inhibit this increase in synthesis. This may help explain in some cases a very clear decrease in blood albumin, with a proteinuria <10 g / 24 hours, while in others, a much larger proteinuria, where blood albumin is normal or moderate reduction.
There is a transport of albumin from the interstitial area into the plasma. But this compensation is also inadequate to restore blood albumin.
ooedema is a common symptom with soft, easily concave (godet mark) nature. ooedema occurs in areas of low interstitial tissue pressure such as around the eye sockets, ankles.
Rarely, can involve the pleura, peritoneum, sometimes causing difficulty breathing. ooedema is caused by salt and water retention due to the following factors:
Mechanism of reducing plasma colloid pressure
This mechanism transports water and electrolytes into the interstitial area and can lead to hypovolemia, and from this hemochromatosis, the effects, physiological, on the nervous - endocrine system (sympathomimetics, RAA, Arginine vasopressin) stimulates tubular reabsorption of water and salt to compensate for the decrease in blood volume.
Specific renal mechanisms
Produced by a decrease in blood albumin or urinary albumin. The salt and water retention in nephrotic syndrome can be explained as follows: Salt (sodium) reabsorption increases very early in the main cells of the manifold because of an increase in the activity of the sodium pump (Na + /). K + / ATPase) and of the epithelial sodium channel.
Increased blood lipids
This abnormality is often seen in nephrotic syndrome. At the beginning, the main increased
Blood cholesterol is the main, increased blood Triglyceride appears secondary then. These Lipide abnormalities are more common when serum albumin decreases <20 g / l.
Low-density lipoprotein (LDL), very low (VLDL) and intermediate type (IDL) all increase, high density lipoprotein (HDL) is normal or decreased.
According to the Fredrickson and Lees classification the most common disorders are type IIa and IIb (60%), followed by type V (30%), and the rarer type III or IV (10%). Lipide abnormalities reversible when nephrotic syndrome disappears.
The mechanism of lipid elevation in nephrotic syndrome is explained by the following factors:
Increased hepatic synthesis of very low-density lipoprotein (VLDL)
This is the main mechanism, often related to the severity of decreased blood albumin. A decrease in plasma colloid pressure stimulates apolipoprotein B synthesis. An increase in HGM CoA reductase, mévalonique acid, cholesterol precursors and free fatty acids, may also be affected.
Reducing yeast Lipoprotein Lipase (LPL)
Plays an important role by reducing the degradation of VLDL. Free fatty acids inhibit the activity of LPL. Apo C II deficiency and héparan sulphate, due to excretion in the urine, also inhibit the activity of this enzyme.
Reducing yeast Lecithin cholesterol acyl transferase (LCAT)
This contributes to lipide abnormalities in nephrotic syndrome by reducing HDL synthesis starting with VLDL.
Loss in urine HDL and apo A1
Urinary loss of HDL and apo A1 has also been reported, but plasma HDL concentrations are mostly normal.
The atherogenic effects of these lipide abnormalities have not been clearly demonstrated, perhaps due to the short duration of nephrotic syndrome progression.
hyperlipidaemia may also facilitate platelet aggregation and thromboembolic complications, and decrease Lymphocyte responses to antigenic stimuli. Hyperlipemia may also be a factor in glomerular fibrosis.
Increased blood clotting
Many haemostasis abnormalities are observed in nephrotic syndrome, which are responsible for increased blood clotting and thromboembolic complications. Increased blood clotting in nephrotic syndrome due to the following mechanisms:
Increased blood fibrinogen due to increased synthesis in the liver.
Increased factors II, V, VII, VIII and X, decreased factors IX, XI, XII due to excretion in urine due to low molecular weight.
Decreased fibrinolytic activity due to decreased plasminogen and increased antiplasmin (alpha 2 macroglobulin, alpha 2 antiplasmin).
Deficiency of coagulant inhibitors (Protein C, antithrombin III).
Increased platelet aggregation.
These abnormalities, combined with hyperlipidaemia and hypovolemia, facilitate the appearance of venous thrombosis and pulmonary embolism.
Increased chance of infection
It appears to be due to a decrease in blood gamma globulin, in addition to a loss of complement in the urine. It is these things that make a mistake of the Lymphocyte response to the antigen.
Malnutrition and growth retardation
In addition to the effects of steroid, malnutrition and growth retardation due to loss of protein and loss of hormones associated with protein carriers (TBG, T3, T4, Vitamin D)
Usually appears quickly, suddenly, oedema may also appear after a mild infection of the nasopharynx.
The nature of oedema: Soft white oedema, concave seal, long imprint retention, systemic oedema, no painful inflammation in the oedema area. There may be fluid in the peritoneum, pleura, pericardium, in the genitals.
Severe complications: pulmonary oedema, laryngeal oedema is common in children.
The amount of urine is usually less than 300-400ml / 24 hours.
Loss of proteinuria: over 3.5gam / 24 hours. It can be from 3 - 10g / 24 hours, in severe cases it can be 30-40g / 24 hours.
The amount of protein increases during standing, during exercise, there is birefringent fat, fat pillars in the urine.
Lipiduria: essentially these are precipitates of Ester Cholesterol. Urea and creatinine urine increased.
Reducing blood protein is very important. Protide blood below 60 g / l, average 50 g / l.
Albumin in blood decreased below 30 g / l, on average 20 g / l. Albumin blood is an accurate indicator to assess the severity of nephrotic syndrome.
Serum globulin disorders:
α2 Globulin increased.
β Globulin increased.
Globulin is usually decreased in nephrotic syndrome alone, and in nephrotic syndrome it may be normal or increase.
Blood cholesterol increased, Phospholipid and Triglycerides increased. Lipid Disorders in Nephrotic Syndrome at the onset of increased cholesterol are key. Hyper Triglycerides appear secondary to follow. Lipid disorders are more common when the blood albumin drops below 20 g / l.
Na + blood and Ca ++ blood decreased.
Increased Haematocrit, increased red blood cells indicate easy blood clotting.
Decreased Antithrombin III due to urinary loss, thrombocytopenia and fibrinogen.
Endocrine Disorders: decreased thyroid hormone if nephrotic syndrome persists.
Implementing the quadrants
Based on clinical and routine tests.
Diagnostic standards are based on the following criteria:
Proteinuria ≥ 3.5g / 24 hours.
Blood protein <60g / l, blood albumin <30g / l.
Blood lipids increased over 900 mg%. Blood cholesterol increased by over 250 mg% or by over 6.5 mmol / l.
Blood protein electrophoresis: decreased albumin, A / G ratio <1, Globulin: α 2 increased, β increased.
Urine has fat pillars, birefringent crystals. In which standards 2 and 3 are mandatory.
Based on renal function investigations:
Pure Nephrotic Syndrome: Kidney function often.
Non-purely nephrotic syndrome: Disorders of glomerular filtration function, renal tubular secretion and reabsorption function.
Of great value in the definitive diagnosis of nephrotic syndrome.
Help classify lesions in nephrotic syndrome accurately.
Nephrotic syndrome in children alone 80% is minimal damage.
Simple and non-simple HCTH:
Simple nephrotic syndrome: normal blood pressure, no kidney failure, no haematuria. Non-purely nephrotic syndrome: increased blood pressure and / or renal failure and / or haematuria. Besides,
also based on Proteinuria electrophoresis: in nephrotic syndrome, proteinuria is mainly
Albumin (Selective Proteinuria).
Oedema of other causes:
Cirrhosis, heart failure, malnutrition oedema.
Skin: Inflammation of subcutaneous tissue.
Peritonitis: Pneumococcal primary peritonitis, but can be caused by other bacteria.
Meningitis: meningitis is rare.
Urinary tract: Urinary tract infections.
Abdominal pain due to nephrotic syndrome
Abdominal pain in nephrotic syndrome due to various causes:
Enteritis caused by infection, possibly by staph.
Due to pancreatic oedema, Treitz ligament oedema or occlusion of the aortic and renal vein.
The most severe hypovolemia is when using powerful diuretics that reduce blood volume and lead to functional acute renal failure. In this case, infusion of Plasma or substances with a high molecular weight is likely to be reversible.
Blood in the state of hypercoagulation: due to decreased Albumin, decreased Antithrombin III, due to increased clotting factors (platelets, fibrinogen). This is a classic complication that accounts for 5-20% of nephrotic syndrome. Often renal, portal vein, pulmonary vein obstruction.
Lack of nutrition
If you get sick at a young age: the child will greatly decrease compared to the same age. Immune reduction, susceptible to infections.
In addition, decreased blood Ca (reduced intestinal Ca reabsorption), Vitamin D metabolism disorder due to protein loss.
Progression and prognosis
It is more likely to happen: if it responds well to treatment, nephrotic syndrome may recover and completely heal. In some cases, the disease recurs many times, many years in a row then recover or switch to chronic kidney failure.
The prognosis depends on
Disease form: pure, not pure.
Pathological lesions of nephrotic syndrome.
Response to treatment.
Treatment of Nephrotic Syndrome includes:
Real life mode.
Treatment of the pathogenesis mechanism.
Primary nephrotic syndrome without hypertension, renal failure and haematuria are often sensitive to corticoids. In a large number of cases, there are no complications in adulthood.
For Nephrotic Syndrome secondary to another condition, the primary treatment remains the primary treatment, the response rate to Corticoids lower than for Primary Nephrotic Syndrome.
Diet rest and eating
Salt restriction depends on the symptoms of oedema.
In the nephrotic syndrome with mild oedema: relative salt restriction (less than 2g / day). Absolute salt restriction (less than 0.5 g / day) in large oedema.
Increase the amount of Protide:
In nephrotic syndrome, the need for Protide is increased due to the loss of a large amount through the urinary tract, so if the patient does not have an increase in blood urea, it is necessary to increase the amount of Protide in the diet above 2g / kg / day. If the patient has renal failure, then the diet will reduce Protide according to the degree of renal failure.
Depending on the degree of oedema and the amount of urine, it is common to limit the amount of water to drink to about 500-700 ml / day.
Treatment of oedema: It should be noted that in nephrotic syndrome, the plasma volume is usually normal or decreased. Therefore, the use of strong diuretics can cause a severe volume loss, which is more likely when the decrease in blood albumin becomes worse (<15g / l). Diuretic treatment should also be used with caution at the beginning. Thiazide diuretics are often the first choice. Potassium-loss diuretics (Spironolactone, triamterene, amiloride) can be used in the case of hypokalaemia. When swelling is severe and does not respond to salt diuretic therapy, loop diuretics are indicated.
Treatment of hyperlipidaemia: in recent years hyperlipidaemia therapy has been recommended in nephrotic syndrome when the disorder is severe. The group of drugs selected here is the Statin group.
Treatment of complications:
Depending on the complications found in a Nephrotic syndrome patient found, for example, in cases of thrombosis, an anticoagulant indication is required.
Add Ca, iron, vitamins, antibiotics if necessary.
Treatment of the pathogenesis mechanism
Corticoids (prednisolone) for adults 1mg / day. Children 1.5mg - 2mg / day.
Attack dose 4 - 8 weeks.
The fortified dose is equal to 1/2 of the attacking dose (0.5mg / kg / day in adults) for 2 - 4 weeks.
Maintenance dose 5 - 10 mg / day.
The duration of the Corticoids course is usually 4.5 to 6 months.
Chlorambucil 2mg tablets, dose of 0.1-0.2 mg / kg for 3 months to 1 year. Can be combined with Corticoids.
Cyclophosphamide (Endoxan) 50mg tablet, 100mg ampoule with starting dose of 5mg / kg / 24h for 12 weeks. Combination with Prednisolone gives good results. When combined, dose of Cyclophosphamide 2.5mg / kg / day for 90 days.
Azathioprine 50mg tablets orally 2-3mg / kg / day for 1-6 months.
Therapeutic immunosuppressants are effective in the cases of nephrotic syndrome alone, in cases of resistance to corticoids, and in cases of corticoids dependence and the type of corticoids contraindicated.
Treat the cause
For secondary nephrotic syndrome, treatment to eliminate the cause is necessary.