Nephrotic syndrome is a condition characterized by heavy leakage of protein in the urine resulting in low levels of the protein (albumin) in the blood. Swelling of the body will occur as a result of this. This syndrome may occur either due to a variety of primary kidney diseases (diseases confined to kidneys) or due to systemic diseases, such as diabetes mellitus.
The kidneys contain special filters called glomeruli to filter out toxic substances and waste products from the blood stream and transfer them to the urine so that they can be removed from the body. These glomeruli, normally allow the free passage of water and small molecular substances into urine but prevent the loss of high molecular weight proteins. Nephrotic syndrome occurs when there is a damage to these filtering units. This damage permits proteins in the blood to leak into the urine, resulting in proteinuria.
WHAT ARE THE DISEASES, WHICH CAN CAUSE NEPHROTIC SYNDROME?
Several diseases can cause nephrotic syndrome. The common one discussed below.
1.Minimal change disease
This is a disease that accounts for 90 percent of cases of the nephrotic syndrome in children under the age of 10, and more than 50 percent of cases in older children. The terms minimal change and nil disease reflect the observation that usual microscopic examination of the kidney tissue is either normal or minimally abnormal. The abnormality becomes apparent only on electron microscopic examination. This disease is thought to result from an abnormal immune process. Patients with minimal change disease produce a protein which damage the glomeruli resulting in nephritoc syndrome.
2. Focal glomerulosclerosis
Focal glomerulosclerosis (FGS) is an important cause of nephrotic syndrome in adults and occasionally in children.
3. Membranous nephropathy
Membranous nephropathy is the second most common cause of primary nephrotic syndrome in adults. Most often it is unrelated to other diseases, although it can be associated with hepatitis B infection, autoimmune diseases, thyroid disease, and the use of certain drugs. An underlying malignancy has been thought to be responsible for some cases of membranous nephropathy in adults, most often a solid tumor.
4.Diabetes mellitus
Kidney disease in patients with diabetes mellitus is a common problem that is most likely to occur in those who have poor blood glucose control or hypertension. Kidney disease in diabetes, initially manifests as minimal proteinuria (microalbuminuria) which subsequently may progress to severe nephrotic syndrome.
5. Systemic lupus erythematosus
Systemic lupus erythematosus (SLE) is a chronic inflammatory disease of unknown cause that can affect the multiple organs of the body, including the kidney. This disease is characterized by the production of a number of antibodies directed against body proteins. Patients with SLE may develop nephrotic syndrome ( For more information, see section of systemic dieases and kidney)
WHAT ARE THE CLINICAL MANIFESTATIONS?
Swelling (Oedema)
Swelling in nephrotic syndrome occurs around the eyes socket upon waking in the morning, and swelling in the feet that becomes prominent after standing up for some time. In severe cases the entire body is swollen with fluid accumulating in the abdominal cavity and chest cavity.
Infection
Patients with the nephrotic syndrome are highly prone to develop infection from a variety of microbial organisms. Pneumococcal infections, especially peritonitis (an infection within the abdomen), and pneumonia are particularly common. Before antibiotics became available, they were the leading cause of death in children with the nephrotic syndrome.
Poor nutrition
Heavy loss of protein in the urine will result in loss of body mass, although the swelling may mask it. Swelling of the mucosa of the gastrointestinal tract will result in loss of appetite and vomiting, which will also contribute to poor nutrition.
Kidney failure
Some patients with the nephrotic syndrome develop a gradual decline in kidney function, which is initially asymptomatic. However, with severe renal failure can occur in nephrotic syndrome though it is rare.
Clotting of blood
Patients with the nephrotic syndrome have an increased risk of developing blood clots which may block blood circulation to vital organs.
Elevated blood lipids
Nephrotic syndrome is associated with elevation of blood lipid levels particularly increased cholesterol levels.
DIAGNOSIS
The diagnosis of nephrotic syndrome is made from a number of tests, including analysis of the urine, blood tests, and a renal (kidney) biopsy. In most cases, a renal biopsy is required to establish the diagnosis.
Urine tests
Examination of a patient’s urine can reveal abnormal amounts of protein in the urine (proteinuria). Protein excretion is generally measured with a 24-hour urine collection. A normal value of protein in the urine is less than 150 mg/day. Patients excreting more than 3.5 g/day are considered to have heavy proteinuria that is in the range of nephrotic syndrome.
Blood tests
A number of blood tests are often indicated in the evaluation of patients who have nephrotic syndrome. The results of some tests can uncover the underlying cause of the nephrotic syndrome, sometimes precluding the need for renal biopsy.
Renal biopsy
Renal biopsy is the standard procedure for determining the cause of heavy proteinuria. Close inspection of tissue obtained will reveal the specific disorder. In children between the age of 2 and12, the most frequent cause of nephrotic syndrome is minimal change disease (in 95 % of the occasions) and renal biopsy is not required. In children, indications for kidney biopsy include; resistance to steroid treatment, frequently relapsing nephrotic syndrome and steroid dependency. Every adult with nephrotic syndrome in the absence of any primary disease should be biopsied.
TREATMENT
Specific treatment
Specific treatment depends on the cause of nephritic syndrome. The exact disorder, which has caused nephritic syndrome can be identified by kidney biopsy and various blood tests.
1. Minimal change disease
Recommended treatment is to give prednisolone 2mg/ Kg on alternate days for 8 weeks. Most patients especially children will respond within 4 weeks. However, it is advisable to give a prolonged treatment, as this will reduce the risk of developing a relapse (another episode of nephrotic syndrome). Adults with minimal change disease may take upto 16 weeks to respond. Oral steroids apart from prednisonole should not be used for the treatment of nephrotic syndrome. Long acting steroids such as dexamethazone and betamethazone are associated with several adverse effects and should be not be considered as alternatives to prednisolone.
In patients, who continue to have nephrotic syndrome after a sufficient course of prednisolone, other drugs such as cyclophosphamide (Endoxan), cyclosporine (Sandimmune or Paniimmune) and mycophenolate (Cellcept) may have to be considered. These drugs can also be considered for patients who have frequently relapsing or steroid dependent nephrotic syndrome.
Recommended course of cyclophosphamide is 2 mg/ Kg daily for 8- 12 weeks. The drug should be taken early in the morning and patient should be instructed to pass urine frequently. Side effect of cyclophosphamide include low blood counts, susceptibility to infection and gonadal toxicity.
Cyclosporine is another option worth considering. Recommended dose is 5 mg/ Kg daily. Cyclosporine is an expensive medicine and patients who have financial constraints can take ketoconazole 50-100 mg daily along with cyclosporine. Ketoconazole inhibits the metabolism of cyclosporine and facilitates the dose reduction of cyclosporine to as low as 0.5-2 mg/Kg daily.
Mycophenolate mofetil (Cellcept) is a novel drug which has become recently available for the treatment of difficult nephrotic syndrome. This drug has shown lot of promise in the treatment of difficult to treat nephritic syndrome.
2. Focal glomerulosclerosis
This disease is much more resistant to therapy in comparison with minimal change nephrotic syndrome. The current recommendation is to give prednisolone at a dose of 2 mg/kg (to a maximum of 120 mg) every other day. A prolonged course of prednisolone may be required to achieve remission. A summary of studies suggests a complete remission rate of approximately 30 percent in all patients and approximately 50 percent in those treated for at least five to eight months. In patients who unresponsive to mycophenolate, cyclosporine or cyclophosphamide may be considered. The alternative approach is to give a combination of low dose prednisolone along with cyclosporine, cyclophosphamide or mycophenolate from the beginning. This will reduce the side effects associated with a prolonged course of steroids.
3. Membranous nephropathy
Optimal therapy for membranous nephropathy is still not clear. Combinations of steroids, cyclosporine, cyclophosphamide and mycophenolate are used with varying degree of success.
4.Diabetes mellitus
The optimal therapy of diabetic kidney disease includes good control of diabetes and hypertension. Drugs such as angiotensin converting inhibitors (Captopril, Ramipril) and angiotensin receptor antagonists have been shown to halt progression of the disease (For more information watch the section on diabetes).
5.Systemic lupus erythematosus
Lupus patients with nephrotic syndrome or signs of progressive renal insufficiency can be treated with corticosteroids and other immunosuppressive agents. Most patients respond well to such a regimen.
General measures
As there is retention of salt (sodium) and water in nephritic syndrome, patients with should restrict the intake of salt and water. Amount of daily salt intake can be reduced to 1-2g depending on the severity of swelling. To reduce the swelling further, diuretics (drugs which increase the excretion of salt and water can be used. Furosemide (Lasix), Spironolactone (aldactone) are frequently used diuretics. Occasionally, diuretics are used in combination. Following points are worth remembering.
->If lasix is used alone it should be twice a day as the action of the drug will last only for few hours.
->When the route of administration of lasix is changed from parenteral (as injection) to oral (through mouth), to get equivalent effect, dose should be doubled.
->Diuretics will not work if salt and water intake are not restricted.
The increase in blood cholesterol that are often seen with the nephrotic syndrome, reverses, when the disease resolves. When the nephrotic syndrome persists, attempts are typically made to lower blood cholesterol. Dietary modification is generally of little benefit, so most patients are initially treated with a lipid lowering drug. These are usually from the class of drugs called ‘statins’.
Thrombotic disease
Some doctors have suggested that anicoagulants (blood thinners) should be given as a preventative measure to the patient with membranous nephropathy due to the increased incidence of blood clots that block blood flow in arteries and veins (thromboemboli). However, this is not standard practice in the usual patient. If thrombosis occurs (ie, a blood clot forms in a blood vessel), the patient is typically treated with blood thinners, such as warfarin (Coumadin), for as long as the nephrotic syndrome persists.
Vaccination
As nephrotic syndrome and its treatment reduces the resistance power of the body, these patients are at a higher risk of developing infections. Infections with Pneumococci (meningitis peritonitis and pneumonia) and H. influenza is particularly common and vaccination should be considered against these bacteriae.