Nephrotic syndrome

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Nephrotic syndrome
Classification and external resources
Diabetic glomerulosclerosis (1) HE.jpg
Histopathological image of diabetic glomerulosclerosis the main cause of nephrotic syndrome in adults. H&E stain.
ICD-10N04
ICD-9581.9
DiseasesDB8905
MedlinePlus000490
eMedicinemed/1612 ped/1564
MeSHD009404
 
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Nephrotic syndrome
Classification and external resources
Diabetic glomerulosclerosis (1) HE.jpg
Histopathological image of diabetic glomerulosclerosis the main cause of nephrotic syndrome in adults. H&E stain.
ICD-10N04
ICD-9581.9
DiseasesDB8905
MedlinePlus000490
eMedicinemed/1612 ped/1564
MeSHD009404

Nephrotic syndrome is a nonspecific kidney disorder characterised by a number of signs of disease: proteinuria, hypoalbuminemia and edema.[1] It is characterized by an increase in permeability of the capillary walls of the glomerulus leading to the presence of high levels of protein passing from the blood into the urine (proteinuria at least 3.5 grams per day per 1.73m2 body surface area);[2] low levels of protein in the blood (hypoproteinemia or hypoalbuminemia), ascites and in some cases, edema; high cholesterol (hyperlipidaemia or hyperlipemia) and a predisposition for coagulation.

The cause is damage to the glomeruli, which can be the cause of the syndrome or caused by it, that alters their capacity to filter the substances transported in the blood. The severity of the damage caused to the kidneys can vary and can lead to complications in other organs and systems. However, patients suffering from the syndrome have a good prognosis under suitable treatment.

Kidneys affected by nephrotic syndrome have small pores in the podocytes, large enough to permit proteinuria (and subsequently hypoalbuminemia,<25g/L, because some of the protein albumin has gone from the blood to the urine) but not large enough to allow cells through (hence no haematuria). By contrast, in nephritic syndrome red blood cells pass through the pores, causing haematuria.

Signs and symptoms[edit]

It is characterized by proteinuria (>3.5g/day), hypoalbuminemia, hyperlipidaemia, and edema (which is generalized and also known as anasarca or dropsy) that begins in the face. Lipiduria (lipids in urine) can also occur, but is not essential for the diagnosis of nephrotic syndrome. Hyponatremia also occurs with a low fractional sodium excretion.

Hyperlipidaemia is caused by two factors:

A few other characteristics seen in nephrotic syndrome are:

Clinical symptoms[edit]

Nephrotic syndrome is usually accompanied by retention of water and sodium. The degree to which this occurs can vary between slight edema in the eyelids that decreases during the day, to affecting the lower limbs, to generalized swelling, to full blown anasarca.[5]

The main symptoms of nephrotic syndrome are:[6]

Pathophysiology[edit]

Drawing of the renal glomerulus.

The renal glomerulus filters the blood that arrives at the kidney. It is formed of capillaries with small pores that allow small molecules to pass through that have a molecular weight of less than 40,000 Daltons,[12] but not larger macromolecules such as proteins.

In nephrotic syndrome, the glomeruli are affected by an inflammation or a hyalinization (the formation of a homogenous crystalline material within cells) that allows proteins such as albumin, antithrombin or the immunoglobulins to pass through the cell membrane and appear in urine.[13]

Albumin is the main protein in the blood that is able to maintain an oncotic pressure, which prevents the leakage of fluid into the extracellular medium and the subsequent formation of edemas.

As a response to hypoproteinemia the liver commences a compensatory mechanism involving the synthesis of proteins, such as alpha-2 macroglobulin and lipoproteins.[13] An increase in the latter can cause the hyperlipidemia associated with this syndrome.

Causes and classification[edit]

Histological image of a normal kidney glomerulus. It is possible to see a glomerulus in the centre of the image surrounded by renal tubules.

Nephrotic syndrome has many causes and may either be the result of a glomerular disease that can be either limited to the kidney, called primary nephrotic syndrome (primary glomerulonephritis), or a condition that affects the kidney and other parts of the body, called secondary nephrotic syndrome.

Primary glomerulonephritis[edit]

Primary causes of nephrotic syndrome are usually described by their histology:[14]

They are considered to be "diagnoses of exclusion", i.e. they are diagnosed only after secondary causes have been excluded.

Secondary glomerulonephritis[edit]

Diabetic glomerulonephritis in a patient with nephrotic syndrome.

Secondary causes of nephrotic syndrome have the same histologic patterns as the primary causes, though they may exhibit some difference suggesting a secondary cause, such as inclusion bodies.[17] They are usually described by the underlying cause.

Secondary causes by histologic pattern[edit]

Membranous nephropathy (MN):

Focal segmental glomerulosclerosis (FSGS)[19]

Minimal change disease (MCD)[19]

Membranoproliferative Glomerulonephritis

Diagnosis[edit]

Urinalysis will be able to detect high levels of proteins and occasionally microscopic haematuria.

Along with obtaining a complete medical history, a series of biochemical tests are required in order to arrive at an accurate diagnosis that verifies the presence of the illness. In addition, imaging of the kidneys (for structure and presence of two kidneys) is sometimes carried out, and/or a biopsy of the kidneys. The first test will be a urinalysis to test for high levels of proteins,[21] as a healthy subject excretes an insignificant amount of protein in their urine. The test will involve a 24-hour bedside urinary total protein estimation. The urine sample is tested for proteinuria (>3.5 g per 1.73 m2 per 24 hours). It is also examined for urinary casts, which are more a feature of active nephritis. Next a blood screen, comprehensive metabolic panel (CMP) will look for hypoalbuminemia: albumin levels of ≤2.5 g/dL (normal=3.5-5 g/dL). Then a [[Renal function#Creatinine Clearance CCr|creatinine clearance]] test will evaluate renal function particularly the glomerular filtration capacity.[22] Creatinine formation is a result of the breakdown of muscular tissue, it is transported in the blood and eliminated in urine. Measuring the concentration of organic compounds in both liquids evaluates the capacity of the glomeruli to filter blood. Electrolytes and urea levels may also be analysed at the same time as creatinine (EUC test) in order to evaluate renal function. A lipid profile will also be carried out as high levels of cholesterol (hypercholesterolemia), specifically elevated LDL, usually with concomitantly elevated VLDL is indicative of nephrotic syndrome.

A kidney biopsy may also be used as a more specific and invasive test method. A study of a sample’s anatomical pathology may then allow the identification of the type of glomerulonephritis involved.[21] However, this procedure is usually reserved for adults as the majority of children suffer from minimum change disease that has a remission rate of 95% with corticosteroids.[23] A biopsy is usually only indicated for children that are corticosteroid resistant as the majority suffer from focal and segmental glomeruloesclerosis.[23]

Further investigations are indicated if the cause is not clear including analysis of auto-immune markers (ANA, ASOT, C3, cryoglobulins, serum electrophoresis), or ultrasound of the whole abdomen.

Classification[edit]

A broad classification of nephrotic syndrome based on underlying cause:

 
 
 
Nephrotic
syndrome
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Primary
 
 
 
Secondary

Nephrotic syndrome is often classified histologically:

 
 
 
 
 
 
 
 
 
 
 
 
Nephrotic syndrome
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MCD
 
 
 
FSGS
 
 
 
MN
 
 
 
MPGN

Differential diagnosis[edit]

Some symptoms that are present in nephrotic syndrome, such as edema and proteinuria, also appear in other illnesses. Therefore, other pathologies need to be excluded in order to arrive at a definitive diagnosis.[24]

Acute fluid overload can cause edema in someone with kidney failure. These people are known to have kidney failure, and have either drunk too much or missed their dialysis. In addition, when Metastatic cancer spreads to the lungs or abdomen it causes effusions and fluid accumulation due to obstruction of lymphatic vessels and veins, as well as serous exudation.

Complications[edit]

Nephrotic syndrome can be associated with a series of complications that can affect an individual’s health and quality of life:[13]

Treatment[edit]

The treatment of nephrotic syndrome can be symptomatic or can directly address the injuries caused to the kidney.

Symptomatic treatment[edit]

The objective of this treatment is to treat the imbalances brought about by the illness:[32] edema, hypoalbuminemia, hyperlipemia, hypercoagulability and infectious complications.

  1. Analyse haemoglobin and haematocrit levels.
  2. A solution of 25% albumin is used that is administered for only 4 hours in order to avoid pulmonary edema.
  3. Haemoglobin and haematocrit levels are analysed again: if the haematocrit value is less than the initial value (a sign of correct expansion) the diuretics are administered for at least 30 minutes. If the haematocrit level is greater than the initial one this is a contraindication for the use of diuretics as they would increase said value.
It may be necessary to give a patient potassium or require a change in dietary habits if the diuretic drug causes hypokalaemia as a side effect.

[41] When the thrombophilia is such that it leads to the formation of blood clots, heparin is given for at least 5 days along with oral anticoagulants (OAC). During this time and if the prothrombin time is within its therapeutic range (between 2 and 3),[42] it may be possible to suspend the LMWH while maintaining the OACs for at least 6 months.[43]

In addition to these key imbalances, vitamin D and calcium are also taken orally in case the alteration of vitamin D causes a severe hypocalcaemia, this treatment has the goal of restoring physiological levels of calcium in the patient.[44]

Treatment of kidney damage[edit]

The treatment of kidney damage may reverse or delay the progression of the disease.[32] Kidney damage is treated by prescribing drugs:

Epidemiology[edit]

Nephrotic syndrome can affect any age, although it is mainly found in adults with a ratio of adults to children of 26 to 1.[47]

The syndrome presents in different ways in the two groups: the most frequent glomerulopathy in children is minimal change disease (66% of cases), followed by focal and segmental glomeruloesclerosis (8%) and mesangiocapillary glomerulonephritis (6%).[17] In adults the most common disease is mesangiocapillary glomerulonephritis (30-40%), followed by focal and segmental glomeruloesclerosis (15-25%) and minimal change disease (20%). The latter usually presents as secondary and not primary as occurs in children. Its main cause is diabetic nephropathy.[17] It usually presents in a patient’s 40s or 50s. Of the glomerulonephritis cases approximately 60% to 80% are primary, while the remainder are secondary.[47]

There are also differences in epidemiology between the sexes, the disease is more common in men than in women by a ratio of 2 to 1.[47]

The epidemiological data also reveals information regarding the most common way that symptoms develop in patients with nephrotic syndrome:[47] spontaneous remission occurs in up to 20% or 30% of cases during the first year of the illness. However, this improvement is not definitive as some 50% to 60% of patients die and / or develop chronic renal failure 6 to 14 years after this remission. On the other hand, between 10% and 20% of patients have continuous episodes of remissions and relapses without dying or jeopardizing their kidney. The main causes of death are cardiovascular, as a result of the chronicity of the syndrome, and thromboembolic accidents.

Prognosis[edit]

The prognosis for nephrotic syndrome under treatment is generally good although this depends on the underlying cause, the age of the patient and their response to treatment. It is usually good in children, because minimal change disease responds very well to steroids and does not cause chronic renal failure. Any relapses that occur become less frequent over time;[48] the opposite occurs with mesangiocapillary glomerulonephritis, in which the kidney fails within three years of the disease developing, making dialysis necessary and subsequent kidney transplant.[48] In addition children under the age of 5 generally have a poorer prognosis than prepubescents, as do adults older than 30 years of age as they have a greater risk of kidney failure.[49]

Other causes such as focal segmental glomerulosclerosis frequently lead to end stage renal disease. Factors associated with a poorer prognosis in these cases include level of proteinuria, blood pressure control and kidney function (GFR).

Without treatment nephrotic syndrome has a very bad prognosis especially rapidly progressing glomerulonephritis, which leads to acute kidney failure after a few months.

See also[edit]

References[edit]

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  2. ^ "ELECTRONIC LEARNING MODULE for KIDNEY and URINARY TRACT DISEASES". Retrieved 2008-11-26. 
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  46. ^ According to MedlinePlus, avascular necrosis is the death of the bone caused by insufficient blood supply to the bone.
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External links[edit]