Nephrotic syndrome (NS) is a condition caused by any of a group of diseases that damage the glomerular leading to increased permeability. It is defined by heavy proteinuira (usually >3g/day), hypoalbuminaemia, hyperlipidemia and oedema.
References: Textbook of Medicine – Souhami and Moxham 2002
Elliot
14 comments:
Signs and Symptoms:
•Hypoalbuminemia
•Oedema – in the extremities, especially around feet and ankles.
•Hypercholesterolemia
•Swollen abdomen
•Facial swelling – around the eyes.
•Foamy appearance of urine
•Unintentional weight gain from fluid retention
•Poor appetite – Can be as a result of hypothyroidism
•High blood pressure
References:
- http://www.nephrologychannel.com/nephrotic/
- http://www.nlm.nih.gov/medlineplus/ency/article/000490.htm
Investigations – Nephrotic Syndrome
Diagnosis of nephrotic syndrome is made mainly on clinical findings. However, investigations can be useful for determining aetiology, and for planning and monitoring treatment.
Full Blood Examination (FBE)
Haemoglobin
Haematocrit (Hct)
Total red blood cells (RBC)
Mean corpuscular volume (MCV)
- average volume of red cells
Mean corpuscular haemoglobin (MCH)
- average amount of haemoglobin in red cells
Mean corpuscular haemoglobin concentration (MCHC)
- average concentration of haemoglobin in red cells
Red cell distribution width (RDW)
- measures variation in red cell size
Platelets
White cells
Neutrophils
Lymphocytes
Monocytes
Eosinophils
Basophils
Erythrocyte sedimentation rate (ESR)
- indicates red cells sticking together due to presence of large proteins (eg. Ig)
In post-infectious nephrotic syndrome, lymphocyte and ESR values may be high.
Sickle-cell anaemia will also show up on the FBE, as well as some malignancies such and lymphoma or leukaemia.
24-Hour Urinalysis
This test is the same as a normal urinalysis, except that all urine produced in a 24 hour period is tested. This allows for more accurate measurements.
Colour
Turbidity (cloudiness)
Specific gravity (concentration of the urine)
pH
Protein
Glucose
Bilirubin
Urobilinogen
Nitrites
Blood
Leukocytes
Nephrotic syndrome shows marked proteinuria, and depending on its cause may also show glucose or leukocytes.
Creatinine Clearance
Creatinine is a natural product of creatine metabolism, and as such has a fairly steady plasma concentration in the body. It is filtered through the glomerulus, and has negligible reabsorption/secretion in the renal tubules (~10%). This means that basically all the creatinine in the urine has passed through the glomerulus. (and the amount that hasn’t can be corrected for as we know it is ~10%)
By measuring the concentration of creatinine in both the plasma and the urine, and measuring urine production, we can determine the glomerular filtration rate (GFR).
The equation is;
Creatinine clearance = [creatinine]urine x urine volume / [creatinine]plasma
Because nephrotic syndrome affects the renal tubules rather than the glomerulus, this figure remains unchanged in nephrotic syndrome. Such a finding helps to rule out other nephropathologies when making a diagnosis.
References
http://mycourses.med.harvard.edu/ResCourses/_online_textbooks/PBD/nrrt.htm
M. Agraharkar, “Nephrotic Syndrome”, Feb 1 2007, from eMedicine
Monash University MED2031 tutorial notes, “Assessment and clinical reasoning for the renal and urinary system”
http://www.health-care-clinic.org/medical-tests/creatinine-clearance.htm
Complications of Nephrotic Syndrome (NS)
• Renal failure : Disease that causes NS can damage glomeruli. Oedema in the legs and fingers might also be occurring in the kidney tissues. These two factors can interfere with the kidneys’ ability to filter blood.
• Thromboembolism: Patients with NS sometimes present with hypercoaguable state in which their blood abnormally overclots. They are at risk of developing blood clots in the legs or in renal vein that transports blood from the kidney.It is also not uncommon when a patient with NS present with pulmonary embolism.
• Infection : NS patients have an increased susceptibility to infection with Streptococcus pneumoniae, Haemophilus influenzae, Escherichia coli, and other gram-negative organisms. Varicella infection is also common. The most common infectious complications are bacterial sepsis, cellulitis, pneumonia, and peritonitis. These complications might be due to decreased immunoglobulin levels, edema fluid acting as a culture medium, protein deficiency, decreased bactericidal activity of the leukocytes, immunosuppressive therapy, decreased perfusion of the spleen caused by hypovolemia, and urinary loss of a complement factor (properdin factor B) that opsonizes certain bacteria.
• Hypovolemia : Hypoalbuminemia decreases the plasma oncotic pressure, resulting in a loss of plasma water into the interstitium and causing a decrease in circulating blood volume. Hypovolemia is generally observed only when the patient's serum albumin level is less than 1.5 g/dL. Symptoms include vomiting, abdominal pain, and diarrhea. The signs include cold hands and feet, delayed capillary filling, oliguria, and tachycardia.
• Failure to thrive may develop in patients with chronic edema, including ascites and pleural effusion. Failure to thrive may be caused by anorexia, hypoproteinemia, increased protein catabolism, or frequent infectious complications. Edema of the gut may cause defective absorption, leading to chronic malnutrition.
• Adverse effects of treatment may occur. Corticosteroids and other immunosuppressive drugs (eg, cyclophosphamide, levamisole, cyclosporin) all have significant adverse effects.
References:
1. eMedicine from Web MD
Available from:http://www.emedicine.com/med/topic1612.htm
2. Nephrology Channel
Available from:http://www.nephrologychannel.com/nephrotic/
robb says….
Nephrotic Syndrome Pathophysiology:
In the normal glomerulus filtration of the blood occurs across a three part filter. The first part consists of the fenestrated (or ‘leaky’) endothelium of the capillaries. The endothelium is continuous with a basal lamina or membrane that is made up of cross-linked collagen and the negatively charged proteoglycan heparan sulphate. This membrane prevents the crossing of small negatively charged proteins. The third part, which is also continuous with the membrane are the secondary processes of the podocytes called pedicels. These pedicels interdigitate to form a barrier with selective slits.
In Nephrotic Syndrome the glomerular permeability to low molecular weight, negatively charged proteins (usually albumin) is increased, leading to increased secretion of protein in the urine. The mechanism for this increased permeability is not entirely known, but centres around two main hypothesises.
The first hypothesis is that the basal lamina is altered (by some sort of damage, there are numerous causes) so that the concentration of negatively charged heparan sulphate in the membrane is lowered, allowing the crossing of anionic proteins. The alternative hypothesis suggests the involvement of the podocyte filtration slits in filtering anionic plasma proteins. It is thought that a specific adhesion molecule, nephrin, is redistributed from the slit pores to the cytoplasm, resulting in retraction, flattening and effacement of the podocytes, and subsequent slit distortions.
In either hypothesis the filtration of small anionic plasma proteins increases, causing proteinuria, and eventually hypoalbuminemia (low levels of albumin in the blood). Even though albumin synthesis rate is not decreased, the capacity to increase production of plasma protein in the liver is insufficient to compensate. The increased levels of protein synthesis in the liver actually contributes to elevated serum lipids. Lipoproteins are synthesized along with the albumin and other proteins lost in the urine, while there is diminished breakdown of lipids caused by reduced levels of lipoprotein lipase.
Oedema is characteristic of nephrotic syndrome. Classically it is thought that reduced plasma protein levels cause the oedema by decreased oncotic pressure. Fluid flow in and out of the vascular system is controlled by Starling’s Law, which is Q = K[(Pp-Pi) – (Op-Oi)], where Q is the net fluid flow, K is the capillary filtration coefficient, Pp and Pi are the hydrostatic pressures of the plasma and interstitium respectively and Op and Oi are the oncotic pressures of the plasma and interstitium. In a normal person, the difference in hydrostatic pressure of the plasma and the interstitium (Pp-Pi) is generally matched by the difference in oncotic pressure of the plasma and interstitium (Op-Oi), resulting in little to no fluid flow into the extracellular space (Averaging along the vascular system). With a decreased plasma oncotic pressure, there is less to drive the fluid back into the vascular system, resulting in a net flow into the extracellular tissue, causing oedema.
Since this would also cause a decrease in plasma volume, then the renin-angiotensin system would be activated, resulting in increased sodium retention and fluid retention, compounding the problem further. However newer research suggests that this is not the case and that the oedema occurs before any significant drop in albumin levels occurs. The exact mechanisms are uncertain, but are thought to be related to increased capillary permeability (increasing the K in Starling’s Law, increasing any small fluid flow) caused by changes in the adhesion proteins of the tight junctions. These junctions may be targeted by abnormal levels of a circulating protein (possibly tumour necrotic factor), while permeability is enhanced by hypoalbuminemia.
References:
Emedicine from Web MD
Deschenes, G, Feraille, E, Doucet, A, Mechanisms of Oedema in nephrotic syndrome: old theories and new ideas, Nephrol Dial Transplant, 2003, 18: 454-456
Management
The goals of management is treat symptoms, prevent complications and delay progression to kidney failure.
Treat underlying cause.
According to the type of kidney disease, treatment to control the cause of nephritic syndrome may be recommended:
1. Nothing – Some cases of nephritic syndrome will improve with time.
2. Steroid tablets e.g. prednisolone – one form of the disease is sensitive to steroid treatment (e.g. membranous nephropathy or focal segmental glomerulonephritis disease)
3. Immunosuppressant – Not commonly used as they can be toxic but can be very effective in some patients.
Treat Symptoms
Fluid retention is managed by diuretics (regularly controlled by
blood tests and weighing)
Give Albumin
Lower blood pressure is important. ACE inhibitors and angiotensin receptor blockers also protect the kidney function and reduce the amount of protein in the urine.
Decrease high cholesterol (if not by diet) with lipid lowering drugs e.g. statin
Blood thinners may be required to prevent clot formation.
References:
Kumar and Clark
Nephrotic Syndrome - http://www.emedicine.com/med/topic1612.htm
Nephrotic Syndrome - http://www.nlm.nih.gov/medlineplus/ency/article/000490.htm
Nephrotic Syndrome - http://renux.dmed.ed.ac.uk/edren/EdRenINFObits/NephroticLong.html#anchor873092
Prognosis of Nephrotic Syndrome:
The prognosis varies depending on the cause of the nephrotic syndrome, the person's age, and the type and degree of kidney damage.
Symptoms may disappear completely if the nephrotic syndrome is caused by a treatable disorder, such as an infection, cancer, or drugs. This situation occurs in about half the cases in children but less often in adults.
If the underlying disorder responds to corticosteroids, sometimes progression of the disease is halted, and less often the condition partially, or rarely, completely reverses.
When the syndrome is caused by HIV infection, it usually progresses relentlessly, often resulting in complete kidney failure in 3 or 4 months.
Children born with the nephrotic syndrome rarely live beyond their first birthday, although a few have survived by means of dialysis treatments or a kidney transplant.
When the cause is systemic lupus erythematosus or diabetes mellitus, treatment with an angiotensin-converting enzyme (ACE) inhibitor often stabilizes or decreases the amount of protein in the urine. However, some people do not respond to treatment with an ACE inhibitor and develop progressive kidney failure within a few years.
In cases of nephrotic syndrome resulting from conditions such as an infection, allergy, or intravenous heroin use, the prognosis varies, depending on how early and effectively the underlying condition is treated.
References:
Nephrotic syndrome
http://www.merck.com/mmhe/sec11/ch144/ch144c.html
Causes of Nephrotic Syndrome
Primary renal pathology
1. Membranous glomerulonephritis
2. Minimal change glomerulonephritis
3. Focal segmental glomerulosclerosis
4. Membranoproliferative glomerulonephritis
5. Crescentric glomerulonephritis
A full explanation of these different glomerulopathies can be found in Kumar and Clark (pp 619-634).
However basically a glomerulopathy is a general term for group of disorders in which,
• There is primarily an immunologically mediated injury to glomeruli, although renal interstitial damage is a regular accompaniment.
• Kidneys are involved symmetrically.
• Secondary mechanisms of glomerular injury come into play following an initial immune insult such as fibrin deposition, platelet aggregation, neutrophil infiltration and free radical induced damage.
Secondary renal pathology
1. Drugs
-catopril (ACE inhibitor)
-penicillamine (immunosuppressor used to treat rheumatoid arthritis, also used as a chelating agent)
-probenecid (uricosuric drug used to treat gout)
-NSAIDs
-heroin
2. Systemic disease
- Systemic Lupus Erythematosus, SLE (chronic autoimmune disease which can affect many organs, renal disease occurs in at least one third of SLE patients)
-Diabetes mellitus
-Amyloidosis (is an acquired or inherited disorder of protein metabolism, in which there is an extracelluar deposition of pathological insoluble proteins in organs and tissues)
3. Malignancy
-carcinoma (CA of an epithelial cell)
-lymphoma (CA of a lymphocyte)
-multiple myeloma (CA of a plasma cell)
4. Infections
-Hepatitis B
-HIV
-Malaria
-Infective endocarditis
5. Allergies
-Vaccines
-Bee stings
Creatinine clearance: Detech. explanation for Hoa
Your kidneys are continuously filtering blood, taking wastes, like urea out and balancing the levels of important salts and water in your body. We'll need to check how well your kidneys are filtering blood and a good way is by measuring creatinine clearance.
Creatinine is a waste that is steadily produced by your muscles and filtered out by the kidneys so the level usually stays about the same in the blood.
By measuring how much creatinine your kidneys can remove over a period of time we can also tell how much blood has been filtered over that period and this is an important measure of kidney health.
Alex.
LIFESTYLE MANAGEMENT
Exercise
Exercise is recommended. However, if it is shown to cause further damage to kidneys, then it may be suitably restricted.
Diet
In order to determine appropriate dietary restrictions, blood tests need to be taken to determine individually specific diets. However, some general rules can be observed.
Protein:
In order to maintain blood homeostasis, in light of poor kidney function, dietary protein should be restricted. Recommended intake is 1.0-1.1g/kg/day if nephritic syndrome is not severe, or else 0.8g/kg/day if syndrome is severe.
Salt:
Salt does not need to be dramatically reduced. 5-7g/day is okay if patient is stable.
General diet:
“Healthier” ie. Low fat (especially saturated fats to control cholesterol levels), low sugar (important in diabetics) high in vitamins, aim to keep weight to optimum level, in order to reduce other risk factors such as blood pressure.
Smoking/Alcohol:
Smoking and alcohol are counter-indicated, as they add extra toxins to the body which can further damage kidneys as well as compromising lung and heart function which affect the kidneys.
X-Rays:
Avoid S-rays that use contrast materials
Medications:
Avoid medications that could damage the kidneys (ie. NSAIDS, or “the triple whammy”)
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REFERENCES
Shirai S, Kimura K. Lifestyle modification and diet therapy for nephrotic syndrome, Nippon Rinsho – MEDLINE, 2004 Oct;62(10):1885-91
http://www.cigna.com/healthinfo/aa124982.html#aa125035
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