Nephrotic syndrome

Nephrology

Clinicals - History

Fact Explanation
Body swelling Nephrotic syndrome is a nonspecific kidney disorder characterised by a number of signs of disease namely proteinuria, hypoalbuminemia and edema. Though it is commoner among pediatric population, it sometimes presents in adults. Males are more susceptible. Nephrotic syndrome can be primarily glomerular in origin or attributed to many secondary causes.
Massive proteinuria causes renal tubulointerstitial inflammation. It results in increased sodium retention that overcomes the physiological mechanisms for removing edema. Increased sodium retention and expanded plasma volume make Renin-angiotensin-aldosterone system less important in developing edema in adult nephrotic syndrome.
Apart from the above methods, the usual pathophysiology mentioned below, that causes edema also helps in developing the body swelling.
Proteins are responsible for the capillary oncotic pressure which is a force that tends to pull water into the circulatory system. As this force is declining, fluid leaks out of the capillaries resulting in excess fluid buildup in the tissues.
Edema in nephrotic syndrome starts in a milder form with progressive bilateral lower extremity swelling. Periorbital swelling is less common in adults. Mild edema can progress into more generalized edema, ascites, pleural effusion and genital edema. Edema has a diurnal variation. Edema is more noticeable in lower extremities later in the day. Periorbital edema, if present, is prominent in the morning. Edema is pitting in nature.
Body swelling
Nephrotic syndrome is a nonspecific kidney disorder characterised by a number of signs of disease namely proteinuria, hypoalbuminemia and edema. Though it is commoner among pediatric population, it sometimes presents in adults. Males are more susceptible. Nephrotic syndrome can be primarily glomerular in origin or attributed to many secondary causes.
Massive proteinuria causes renal tubulointerstitial inflammation. It results in increased sodium retention that overcomes the physiological mechanisms for removing edema. Increased sodium retention and expanded plasma volume make Renin-angiotensin-aldosterone system less important in developing edema in adult nephrotic syndrome.
Apart from the above methods, the usual pathophysiology mentioned below, that causes edema also helps in developing the body swelling.
Proteins are responsible for the capillary oncotic pressure which is a force that tends to pull water into the circulatory system. As this force is declining, fluid leaks out of the capillaries resulting in excess fluid buildup in the tissues.
Edema in nephrotic syndrome starts in a milder form with progressive bilateral lower extremity swelling. Periorbital swelling is less common in adults. Mild edema can progress into more generalized edema, ascites, pleural effusion and genital edema. Edema has a diurnal variation. Edema is more noticeable in lower extremities later in the day. Periorbital edema, if present, is prominent in the morning. Edema is pitting in nature.
Frothy urine Glomerular capillary membrane is damaged by several less clear mechanisms which increases its permeability. Though the exact cause remains unknown, disturbances in immune system or genetic mutations are thought to causes extensive effacement of podocyte foot processes. The increased permeability permits proteins such as albumin, antithrombin or immunoglobulins to pass through the cell membrane and appear in urine.
Another hypothesis is that the reduction of negative charge of the glycoproteins within the glomerular capillary wall. So the usual repulsion forces which had between negatively charged glomerular capillary wall and albumin molecules diminished leading to increase permeability of the wall for protein molecules. Appearance of proteins in "nephrotic levels" causes frothy urine. (more than 40mg/m2/hour or urine protein : creatinine ratio more than 200mg protein/mmol creatinine). Frothy urine may accompany with hematuria in adults especially in the sub types like focal segmental glomerulosclerosis (FSGS) which is the most common pathological sub type. Pathologically it appears as sclerosis/scarring of parts of some glomeruli. There are several pathological variants of FSGS seen on biopsy. Collapsing, glomerular tip lesion, cellular variant and perihilar variant are among them. The collapsing variant is associated with higher rate of progression to end-stage renal disease. Mesangial proliferative glomerulonephritis (MPGN) is the inflammation of the glomeruli along with the deposit of antibodies in their membranes. Membranous glomerulonephritis and rapidly progressive glomerulonephritis are other rare subtypes. All these types can present with proteinuria and/or hematuria.
In minimal change nephrotic syndrome, the commonest pediatric form, though rarer in adult almost always manifest with pure proteinuria.
Frothy urine
Glomerular capillary membrane is damaged by several less clear mechanisms which increases its permeability. Though the exact cause remains unknown, disturbances in immune system or genetic mutations are thought to causes extensive effacement of podocyte foot processes. The increased permeability permits proteins such as albumin, antithrombin or immunoglobulins to pass through the cell membrane and appear in urine.
Another hypothesis is that the reduction of negative charge of the glycoproteins within the glomerular capillary wall. So the usual repulsion forces which had between negatively charged glomerular capillary wall and albumin molecules diminished leading to increase permeability of the wall for protein molecules. Appearance of proteins in "nephrotic levels" causes frothy urine. (more than 40mg/m2/hour or urine protein : creatinine ratio more than 200mg protein/mmol creatinine). Frothy urine may accompany with hematuria in adults especially in the sub types like focal segmental glomerulosclerosis (FSGS) which is the most common pathological sub type. Pathologically it appears as sclerosis/scarring of parts of some glomeruli. There are several pathological variants of FSGS seen on biopsy. Collapsing, glomerular tip lesion, cellular variant and perihilar variant are among them. The collapsing variant is associated with higher rate of progression to end-stage renal disease. Mesangial proliferative glomerulonephritis (MPGN) is the inflammation of the glomeruli along with the deposit of antibodies in their membranes. Membranous glomerulonephritis and rapidly progressive glomerulonephritis are other rare subtypes. All these types can present with proteinuria and/or hematuria.
In minimal change nephrotic syndrome, the commonest pediatric form, though rarer in adult almost always manifest with pure proteinuria.
Weight gain Excessive fluid accumulation in intravascular and interstitial space lead to considerably increased body weight in some individuals. Weight gain
Excessive fluid accumulation in intravascular and interstitial space lead to considerably increased body weight in some individuals.
Fatigue and loss of appetite Long term kidney disease tends to cause anemia as the disease course may affect production of Erythropoietin, a glycoprotein hormone that controls erythropoiesis which is produced by interstitial fibroblasts in the kidney. Fatigue and loss of appetite
Long term kidney disease tends to cause anemia as the disease course may affect production of Erythropoietin, a glycoprotein hormone that controls erythropoiesis which is produced by interstitial fibroblasts in the kidney.
Reduced urine output Excessive extravasation of fluids may results in hypovolemia. Hypovolemia and reduced renal perfusion pressure cause reduced urine output. Rarely Renin-angiotensin-aldosterone system and ADH hormone aggravate it. Reduced urine output
Excessive extravasation of fluids may results in hypovolemia. Hypovolemia and reduced renal perfusion pressure cause reduced urine output. Rarely Renin-angiotensin-aldosterone system and ADH hormone aggravate it.
Red colored urine Adult nephrotic syndrome is divided into two clinical sub types. "Nephrotic syndrome with bland urinary sediment" is the common form which manifest as proteinuria without active sediments such as red cells or red cell casts. "Nephrotic syndrome with active urinary sediment" is a mixed scenario with both proteinuria and hematuria. Hematuria is evident in some sub types of nephrotic syndrome such as focal segmental glomerulosclerosis (most common pathological form of nephrotic syndrome in adults), mesangial proliferative, membranous nephropathy and mesangial capillary glomerulonephritis. However this is rare, but not as rare as in pediatric patients. Red colored urine
Adult nephrotic syndrome is divided into two clinical sub types. "Nephrotic syndrome with bland urinary sediment" is the common form which manifest as proteinuria without active sediments such as red cells or red cell casts. "Nephrotic syndrome with active urinary sediment" is a mixed scenario with both proteinuria and hematuria. Hematuria is evident in some sub types of nephrotic syndrome such as focal segmental glomerulosclerosis (most common pathological form of nephrotic syndrome in adults), mesangial proliferative, membranous nephropathy and mesangial capillary glomerulonephritis. However this is rare, but not as rare as in pediatric patients.
Fever Patients with nephrotic syndrome are more susceptible for infections as their immunity has been declined secondary to urinary loss of IgG immunoglobulin. Effect of steroid therapy,reduced compliment and T cell function or impaired phagocytic function may contribute.
Therefore the patient may suffer from any sort of infection such as cellulitis, peritonitis or sepsis. The risk of infection in adults is less severe than in children. It may rise in adults who have many relapses and who are on longer term corticosteroid therapy.
Fever
Patients with nephrotic syndrome are more susceptible for infections as their immunity has been declined secondary to urinary loss of IgG immunoglobulin. Effect of steroid therapy,reduced compliment and T cell function or impaired phagocytic function may contribute.
Therefore the patient may suffer from any sort of infection such as cellulitis, peritonitis or sepsis. The risk of infection in adults is less severe than in children. It may rise in adults who have many relapses and who are on longer term corticosteroid therapy.
Abdominal pain Abdominal pain may present due to several etiologies in nephrotic syndrome. Uncompensated hypovolemia, peritonitis (as a result of susceptibility of infection secondary to low immunoglobulin level), cellulitis and renal vein thrombosis can cause abdominal pain. Abdominal pain
Abdominal pain may present due to several etiologies in nephrotic syndrome. Uncompensated hypovolemia, peritonitis (as a result of susceptibility of infection secondary to low immunoglobulin level), cellulitis and renal vein thrombosis can cause abdominal pain.
Difficulty in breathing Massive ascites and thoracic compression, frank pulmonary edema or pulmonary effusions as a result of transudation of fluids into body cavities may cause difficulty in breathing. Increased prothrombotic state )thrombocytosis, hemoconcentration, relative immobilization) and decreased fibrinolytic factors (urinary loss of antithrombin protein C and S) result increased risk of venous and arterial thromboembolism. Pulmonary embolism risk is also increased. Difficulty in breathing
Massive ascites and thoracic compression, frank pulmonary edema or pulmonary effusions as a result of transudation of fluids into body cavities may cause difficulty in breathing. Increased prothrombotic state )thrombocytosis, hemoconcentration, relative immobilization) and decreased fibrinolytic factors (urinary loss of antithrombin protein C and S) result increased risk of venous and arterial thromboembolism. Pulmonary embolism risk is also increased.
Secondary causes Diabetes, systemic vasculitides like SLE,
amyloidosis, myeloma, infections such as malaria, HIV, Drugs such as Penicillamine, Captopril in high dose, gold, metals like Mercury, Cadmium, allergies and pre-eclampsia can results in nephrotic syndrome.
Secondary causes
Diabetes, systemic vasculitides like SLE,
amyloidosis, myeloma, infections such as malaria, HIV, Drugs such as Penicillamine, Captopril in high dose, gold, metals like Mercury, Cadmium, allergies and pre-eclampsia can results in nephrotic syndrome.
Past history of similar episodes Some adult patients admit to the ward with relapses of nephrotic syndrome. They may have one or more similar episodes most of the time. Past history of similar episodes
Some adult patients admit to the ward with relapses of nephrotic syndrome. They may have one or more similar episodes most of the time.

Clinicals - Examination

Fact Explanation
Anthropometry Steroid treatment and generalized edema cause weight gain. Anthropometry
Steroid treatment and generalized edema cause weight gain.
Edema Pitting edema distributes more in lower extremities and peri orbital area. It may progress to a generalized edema later causing ascites, pleural effusion and genital edema. Edema
Pitting edema distributes more in lower extremities and peri orbital area. It may progress to a generalized edema later causing ascites, pleural effusion and genital edema.
Fever Nephrotic syndrome poses high risk of infection as patient has become immunocompromised due to urinary loss of IgG immunoglobulin. Steroids affects humoral and innate immunity too. Therefore the patient may suffer from any sort of infection such as cellulitis, peritonitis or sepsis which may manifest as fever. Fever
Nephrotic syndrome poses high risk of infection as patient has become immunocompromised due to urinary loss of IgG immunoglobulin. Steroids affects humoral and innate immunity too. Therefore the patient may suffer from any sort of infection such as cellulitis, peritonitis or sepsis which may manifest as fever.
pallor Chronic kidney disease tends to cause anemia as the disease course may affect production of erythropoietin which controls erythropoiesis. Erythropoietin is produced by interstitial fibroblasts in the kidney. pallor
Chronic kidney disease tends to cause anemia as the disease course may affect production of erythropoietin which controls erythropoiesis. Erythropoietin is produced by interstitial fibroblasts in the kidney.
Features of hypothyroidism Hypothyroidism should be excluded as an important differential diagnosis. Depression, slow heart rate, unexplained weight gain, intolerance to cold temperatures,fatigued and aching muscles, dry, coarse skin and puffy face are important signs and symptoms. Features of hypothyroidism
Hypothyroidism should be excluded as an important differential diagnosis. Depression, slow heart rate, unexplained weight gain, intolerance to cold temperatures,fatigued and aching muscles, dry, coarse skin and puffy face are important signs and symptoms.
Hypertension In adults with nephrotic syndrome, hypertension can be due to intravascular fluid overload secondary to sodium retention.Or else it rarely occurs either due to the extreme vasoconstrictive response to hypovolemia or the nature of the underlying pathology such as in mesangioproliferative sub type. Hypertension
In adults with nephrotic syndrome, hypertension can be due to intravascular fluid overload secondary to sodium retention.Or else it rarely occurs either due to the extreme vasoconstrictive response to hypovolemia or the nature of the underlying pathology such as in mesangioproliferative sub type.
Signs of respiratory distress and pleural effusion Rapid, shallow breathing, grunting, flaring of the nostrils and intercostal/subcostal recessions are common findings suggestive of respiratory distress. Massive ascites, pulmonary edema, pulmonary effusions or pulmonary embolism can cause respiratory distress. Signs of respiratory distress and pleural effusion
Rapid, shallow breathing, grunting, flaring of the nostrils and intercostal/subcostal recessions are common findings suggestive of respiratory distress. Massive ascites, pulmonary edema, pulmonary effusions or pulmonary embolism can cause respiratory distress.
Abdominal tenderness Cellulitis, peritonitis, renal vein thrombosis or hypovolemia can lead to abdominal tenderness. Abdominal tenderness
Cellulitis, peritonitis, renal vein thrombosis or hypovolemia can lead to abdominal tenderness.
Features of diabetic complications In the case of long standing diabetes, there may be diabetic retinopathy ( blurred vision, distortion, floaters,and progressive visual acuity loss), which correlates closely with diabetic nephropathy. Patient may show features of neuropathy as well. (distal sensory, motor, entrapment or non compressive neuropathies) Features of diabetic complications
In the case of long standing diabetes, there may be diabetic retinopathy ( blurred vision, distortion, floaters,and progressive visual acuity loss), which correlates closely with diabetic nephropathy. Patient may show features of neuropathy as well. (distal sensory, motor, entrapment or non compressive neuropathies)
Features of other secondary causes Eg-
SLE (Anemia, photosensitivity, pericardial or pleural effusion, rash)
Amyloidosis (Cardiomyopathy, hepatomegaly, peripheral neuropathy)
Features of other secondary causes
Eg-
SLE (Anemia, photosensitivity, pericardial or pleural effusion, rash)
Amyloidosis (Cardiomyopathy, hepatomegaly, peripheral neuropathy)

Investigations - Diagnosis

Fact Explanation
Urine ward test This test offers a qualitative assessment of Urine protein to creatinine ratio. It is usually more than 3+ in nephrotic syndrome. This can be done using commercial urine strips for protein or by urine heat coagulation test. Urine should be collector to fill 2/3 of test tube. The upper part of the tube should be heated. If a turbidity is formed few drops of sodium salicylate or vinegar and see if the turbidity disappears. Quantification of the amount of protein can be done according to the following scale. Nil - No turbidity. Trace - Turbid but no difficulty in reading print. 1+ - Turbid. 2+ - Turbid, can't read, but can notice black. 3+ - Turbid, can't notice black. 4+ - Precipitate. This can also be done with urine dipstick test. Urine ward test
This test offers a qualitative assessment of Urine protein to creatinine ratio. It is usually more than 3+ in nephrotic syndrome. This can be done using commercial urine strips for protein or by urine heat coagulation test. Urine should be collector to fill 2/3 of test tube. The upper part of the tube should be heated. If a turbidity is formed few drops of sodium salicylate or vinegar and see if the turbidity disappears. Quantification of the amount of protein can be done according to the following scale. Nil - No turbidity. Trace - Turbid but no difficulty in reading print. 1+ - Turbid. 2+ - Turbid, can't read, but can notice black. 3+ - Turbid, can't notice black. 4+ - Precipitate. This can also be done with urine dipstick test.
24 hours urine collection for protein estimation A level of more than 40 mg per square meter pe hour defines nephrotic-range proteinuria. 24 hours urine collection for protein estimation
A level of more than 40 mg per square meter pe hour defines nephrotic-range proteinuria.
Serum protein Serum albumin level is less than 25g per liter. Serum protein
Serum albumin level is less than 25g per liter.
Lipid profile Elevated total cholesterol and low-density lipoproteins are common findings. Triglycerides are elevated in around 50% of cases. High-density lipoproteins are almost always normal. Hypoproteinemia is thought to trigger increased production of lipoproteins in liver as a compensatory reaction. Lipid profile
Elevated total cholesterol and low-density lipoproteins are common findings. Triglycerides are elevated in around 50% of cases. High-density lipoproteins are almost always normal. Hypoproteinemia is thought to trigger increased production of lipoproteins in liver as a compensatory reaction.
Urine protein to creatinine ratio A urine protein/creatinine ratio of more than 3 mg/mg or more than 200 mg/mmol is equivalent with nephrotic-range proteinuria. Urine protein to creatinine ratio
A urine protein/creatinine ratio of more than 3 mg/mg or more than 200 mg/mmol is equivalent with nephrotic-range proteinuria.
Urine full report Proteinuria equal or more than 2+, microscopic hematuria and hyaline casts are usual findings of urine full report. Urine full report
Proteinuria equal or more than 2+, microscopic hematuria and hyaline casts are usual findings of urine full report.
Serum creatinine or glomerular filtration rate This is used to rule out acute kidney failure. Serum creatinine or glomerular filtration rate
This is used to rule out acute kidney failure.
Fasting blood sugar To exclude diabetes mellitus as a cause for secondary nephrotic syndrome or to evaluate the control of diabetes in an already diagnosed individual. Fasting blood sugar
To exclude diabetes mellitus as a cause for secondary nephrotic syndrome or to evaluate the control of diabetes in an already diagnosed individual.
Hepatitis B surface antigen and hepatitis C antibody To exclude hepatitis as a cause for secondary nephrotic syndrome. Hepatitis B surface antigen and hepatitis C antibody
To exclude hepatitis as a cause for secondary nephrotic syndrome.
Anti-nuclear antibody (ANA) To exclude connective tissue diseases like SLE as a cause for secondary nephrotic syndrome. Anti-nuclear antibody (ANA)
To exclude connective tissue diseases like SLE as a cause for secondary nephrotic syndrome.
Serum electrophoresis Reduction of albumin and rise in α2 globulin are electrophoresis findings of nephrotic syndrome. Serum electrophoresis is important to exclude myeloma of which a monoclonal paraprotein band with immune paresis is characteristic. Serum electrophoresis
Reduction of albumin and rise in α2 globulin are electrophoresis findings of nephrotic syndrome. Serum electrophoresis is important to exclude myeloma of which a monoclonal paraprotein band with immune paresis is characteristic.
Renal biopsy Renal biopsy is Indicated when doubts arise regarding the presence of minimal change nephrotic syndrome. Renal biopsy is also helpful to assess disease activity or to confirm diagnosis of diseases such as amyloidosis or SLE. Renal biopsy is not indicated in a patient with long standing, insulin dependant diabetes mellitus with retinopathy and/or neuropathy. It is also not recommended in drug induced nephrotic syndrome where the suspecting drug should be stopped first or in young children whose disease is most probably due to minimal change disease. Renal biopsy
Renal biopsy is Indicated when doubts arise regarding the presence of minimal change nephrotic syndrome. Renal biopsy is also helpful to assess disease activity or to confirm diagnosis of diseases such as amyloidosis or SLE. Renal biopsy is not indicated in a patient with long standing, insulin dependant diabetes mellitus with retinopathy and/or neuropathy. It is also not recommended in drug induced nephrotic syndrome where the suspecting drug should be stopped first or in young children whose disease is most probably due to minimal change disease.
Renal ultrasonography This is not usually helpful in assessing a patient with nephrotic syndrome. But it may identify renal venous thrombosis if suggestive features such as flank pain, hematuria or acute renal failure are present. Renal ultrasonography
This is not usually helpful in assessing a patient with nephrotic syndrome. But it may identify renal venous thrombosis if suggestive features such as flank pain, hematuria or acute renal failure are present.

Investigations - Management

Fact Explanation
Serum creatinine Renal function tests should be done when the patient is on cyclosporine due to its nephrotoxicity. Serum creatinine
Renal function tests should be done when the patient is on cyclosporine due to its nephrotoxicity.
White blood cell count Most of the immunosuppressive treatment regimes should be closely monitored with white blood cell count due to the risk of neutropenia. When the patient is on Cyclophosphamide, if leukopenia occurs the therapy should be discontinued and recommenced once the recovers. If neutropenia appears, permanent discontinuation of levamisole should be done. White blood cell count
Most of the immunosuppressive treatment regimes should be closely monitored with white blood cell count due to the risk of neutropenia. When the patient is on Cyclophosphamide, if leukopenia occurs the therapy should be discontinued and recommenced once the recovers. If neutropenia appears, permanent discontinuation of levamisole should be done.

Management - Supportive

Fact Explanation
Monitoring Body weight, input and output, temperature chart and postural blood pressure should be monitored daily or in higher frequency. Serum creatinine and blood urea nitrogen or serum electrolytes should be monitored every other day. These are recorded in order to assess the disease progression and predict complications such as infections, renal failure and shock. Monitoring
Body weight, input and output, temperature chart and postural blood pressure should be monitored daily or in higher frequency. Serum creatinine and blood urea nitrogen or serum electrolytes should be monitored every other day. These are recorded in order to assess the disease progression and predict complications such as infections, renal failure and shock.
Bed rest Bed rest is recommended only if the patient has severe edema or severe hypertension. Otherwise it is not encouraged as it can pose an added risk of thromboembolism. Bed rest
Bed rest is recommended only if the patient has severe edema or severe hypertension. Otherwise it is not encouraged as it can pose an added risk of thromboembolism.
Nutrition Normal protein diet with adequate calories and restricted salt content (approximately 3g salt per day) is recommended until the resolution of the relapse. High protein diet is not encouraged. Fluid restriction may be necessary to less than 1.5 liters per day as the fluid overload risk is high in adults. Nutrition
Normal protein diet with adequate calories and restricted salt content (approximately 3g salt per day) is recommended until the resolution of the relapse. High protein diet is not encouraged. Fluid restriction may be necessary to less than 1.5 liters per day as the fluid overload risk is high in adults.
Antibiotics Prophylactic oral penicillin is of less value in prevention of primary bacterial peritonitis. So, it is not usually recommended. Antibiotics
Prophylactic oral penicillin is of less value in prevention of primary bacterial peritonitis. So, it is not usually recommended.
Vaccination Pneumococcal vaccination has been recommended for patients with nephrotic syndrome due to their immunocompromised state as a result of prolonged prednisolone therapy. Vaccination
Pneumococcal vaccination has been recommended for patients with nephrotic syndrome due to their immunocompromised state as a result of prolonged prednisolone therapy.
Diuretics Furosemide is a potent loop diuretic which acts on ascending thick loop of Henle.
A high dose of frusemide (80 - 120 mg) is required. Administration is usually intravenous as oral route is not effective owing to the poor absorption of oral drugs caused by intestinal edema. To further reduce sodium reabsorption in distal nephron, Furosemide can be combined with thiazide or potassium sparing diuretics. Oedema should be reversed slowly as rapid natriuresis leads to hypovolemia, acute renal failure and haemoconcentration.
Diuretics
Furosemide is a potent loop diuretic which acts on ascending thick loop of Henle.
A high dose of frusemide (80 - 120 mg) is required. Administration is usually intravenous as oral route is not effective owing to the poor absorption of oral drugs caused by intestinal edema. To further reduce sodium reabsorption in distal nephron, Furosemide can be combined with thiazide or potassium sparing diuretics. Oedema should be reversed slowly as rapid natriuresis leads to hypovolemia, acute renal failure and haemoconcentration.
Albumin infusion Intravenous albumin can aid To expand plasma volume (only if symptomatic hypovolemia is present) and diuresis when edema may be caused by hypoalbuminemia. But lack of evidence, side effects and high cost limit its use. Albumin infusion
Intravenous albumin can aid To expand plasma volume (only if symptomatic hypovolemia is present) and diuresis when edema may be caused by hypoalbuminemia. But lack of evidence, side effects and high cost limit its use.
Antihypertensives Most persons with nephrotic syndrome should be started on Angiotensin-converting enzyme (ACE) inhibitors treatment to reduce proteinuria, regardless of blood pressure. ACEIs reduce proteinuria and reduce the risk of progression to renal disease in persons with nephrotic syndrome. Antihypertensives
Most persons with nephrotic syndrome should be started on Angiotensin-converting enzyme (ACE) inhibitors treatment to reduce proteinuria, regardless of blood pressure. ACEIs reduce proteinuria and reduce the risk of progression to renal disease in persons with nephrotic syndrome.
Management of hyperlipidemia It is sometimes recommended when increased risk of atherogenesis or myocardial infarction in persons with nephrotic syndrome, possibly related to increased lipid levels. But evidences are lack regarding routine use of lipid lowering drugs. Management of hyperlipidemia
It is sometimes recommended when increased risk of atherogenesis or myocardial infarction in persons with nephrotic syndrome, possibly related to increased lipid levels. But evidences are lack regarding routine use of lipid lowering drugs.
Prevention and management of thromboembolism It is advisable to remain alert for signs or symptoms suggesting thromboembolism than using prophylaxis. If it is diagnosed he/she should be treated with heparin or low molecular weight heparin. In a high risk patient, usage of heparin, low molecular weight heparin or graduated pressure stockings can be considered. Prevention and management of thromboembolism
It is advisable to remain alert for signs or symptoms suggesting thromboembolism than using prophylaxis. If it is diagnosed he/she should be treated with heparin or low molecular weight heparin. In a high risk patient, usage of heparin, low molecular weight heparin or graduated pressure stockings can be considered.
Management of sepsis In a patient who developed peritonitis, early detection and aggressive management with antibiotics such as parenteral benzylpenicillin and a third generation cephalosporin should be started. Management of sepsis
In a patient who developed peritonitis, early detection and aggressive management with antibiotics such as parenteral benzylpenicillin and a third generation cephalosporin should be started.
Ophthalmology referral Frequent eye check ups should be done when the patient is on prednisolone as it increases risk of developing scleritis and corneal thinning. Ophthalmology referral
Frequent eye check ups should be done when the patient is on prednisolone as it increases risk of developing scleritis and corneal thinning.
Calcium supplementation Hypocalcemia is a side effect of prednisolone due to its hyper calciuric effect. So calcium supplementation is recommended for patients with long term steroid therapy. Calcium supplementation
Hypocalcemia is a side effect of prednisolone due to its hyper calciuric effect. So calcium supplementation is recommended for patients with long term steroid therapy.
Patient education Parents or caregivers should be thoroughly educated regarding the disease, prognosis, drugs and side effects, lifestyle modifications and complications of the disease as the knowledge of a chronic disease like nephrotic syndrome is paramount in successful management. Nephrotic syndrome should be introduced as a chronic relapsing disease. And they must be reassured that progression of this disease to a chronic kidney disease is extremely rare with adequate management.
Patient should be educated regarding prednisolone or any other alkylating agent used. The importance of steroids even in the presence of side effects should be emphasized. The risk of addisonian crisis if abrupt withdrawal of steroids should be informed. Early medical attention should be obtained in case of an infection. Patient should avoid crowded places due to risk of infections. And he/she should be admitted to the hospital if there is edema or protein greater than or equal to 2 for more than 2 days at home. patient should be followed up at clinic frequently with urine protein test records.
Patient education
Parents or caregivers should be thoroughly educated regarding the disease, prognosis, drugs and side effects, lifestyle modifications and complications of the disease as the knowledge of a chronic disease like nephrotic syndrome is paramount in successful management. Nephrotic syndrome should be introduced as a chronic relapsing disease. And they must be reassured that progression of this disease to a chronic kidney disease is extremely rare with adequate management.
Patient should be educated regarding prednisolone or any other alkylating agent used. The importance of steroids even in the presence of side effects should be emphasized. The risk of addisonian crisis if abrupt withdrawal of steroids should be informed. Early medical attention should be obtained in case of an infection. Patient should avoid crowded places due to risk of infections. And he/she should be admitted to the hospital if there is edema or protein greater than or equal to 2 for more than 2 days at home. patient should be followed up at clinic frequently with urine protein test records.

Management - Specific

Fact Explanation
Steroid therapy Classically, minimal change disease responds better to corticosteroids than in other pathological forms. Management of minimal change nephropathy aims at reversing abnormal urinary protein leak. This can be achieved by high dose steroids therapy for 8 weeks. The exact duration is not explained. But it is accepted that adults require longer course of steroids. Though more than 95% of children respond well for steroid therapy
response of adults is less.
Some patients achieve spontaneous remissions. If remission lasts more than 4 years, relapse is rare.
However the treatment with corticosteroids remains controversial in the management of nephrotic syndrome in adults. Possible side-effects of prednisolone include diabetes mellitus, Adrenal suppression, Acne, delayed wound healing, ulcerative esophagitis, GI perforation, peptic ulcer, hypokalemic alkalosis, myopathy, insomnia, psychosis, seizure, urticaria, vertigo and weight gain.
Steroid therapy
Classically, minimal change disease responds better to corticosteroids than in other pathological forms. Management of minimal change nephropathy aims at reversing abnormal urinary protein leak. This can be achieved by high dose steroids therapy for 8 weeks. The exact duration is not explained. But it is accepted that adults require longer course of steroids. Though more than 95% of children respond well for steroid therapy
response of adults is less.
Some patients achieve spontaneous remissions. If remission lasts more than 4 years, relapse is rare.
However the treatment with corticosteroids remains controversial in the management of nephrotic syndrome in adults. Possible side-effects of prednisolone include diabetes mellitus, Adrenal suppression, Acne, delayed wound healing, ulcerative esophagitis, GI perforation, peptic ulcer, hypokalemic alkalosis, myopathy, insomnia, psychosis, seizure, urticaria, vertigo and weight gain.
Cyclophosphamide Cyclophosphamide prolongs the duration of remission in steroid-resistant nephrotic syndrome and reduces the number of relapses in Steroid-dependent nephrotic syndrome. Patient should be adequately hydrated before commencement of the drug as hemorrhagic cystitis is a possible side effect. white blood cell count should be monitored frequently to detect leucopenia early. Cyclophosphamide may cause infertility in males. Cyclophosphamide
Cyclophosphamide prolongs the duration of remission in steroid-resistant nephrotic syndrome and reduces the number of relapses in Steroid-dependent nephrotic syndrome. Patient should be adequately hydrated before commencement of the drug as hemorrhagic cystitis is a possible side effect. white blood cell count should be monitored frequently to detect leucopenia early. Cyclophosphamide may cause infertility in males.
Cyclosporine It is need to do renal biopsy prior the commencement of Cyclosporine as it can change the architecture of the glomerulus. Hypertension, nephrotoxicity, hirsutism and gingival hyperplasia are common side effects. Renal function should be monitored closely. Cyclosporine
It is need to do renal biopsy prior the commencement of Cyclosporine as it can change the architecture of the glomerulus. Hypertension, nephrotoxicity, hirsutism and gingival hyperplasia are common side effects. Renal function should be monitored closely.
Chlorambucil It is another alkylating agent that can cause reversible pancytopenia. Chlorambucil
It is another alkylating agent that can cause reversible pancytopenia.
Nephrectomy and renal transplantation In a few individuals, proteinuria remains torrential despite aggressive treatment. Hypotension and oedema persist. The plasma creatinine increases and protein malnutrition becomes increasingly severe. Surgical or medical nephrectomy is advisable in such patient. Medical nephrectomy is achieved in intractable nephrotic syndrome by bilateral embolization of renal arteries. This should be followed by renal transplantation which is a successful treatment option for adult patients who are mentioned above and those who reach end stage renal disease. But sometimes nephrotic syndrome recurs in the transplanted kidney. Hemodialysis and peritoneal dialysis are the other possible options for renal replacement.
Congenital nephrotic syndrome is a rare and uniformly fatal disease which needs renal transplantation in pediatric group.
Nephrectomy and renal transplantation
In a few individuals, proteinuria remains torrential despite aggressive treatment. Hypotension and oedema persist. The plasma creatinine increases and protein malnutrition becomes increasingly severe. Surgical or medical nephrectomy is advisable in such patient. Medical nephrectomy is achieved in intractable nephrotic syndrome by bilateral embolization of renal arteries. This should be followed by renal transplantation which is a successful treatment option for adult patients who are mentioned above and those who reach end stage renal disease. But sometimes nephrotic syndrome recurs in the transplanted kidney. Hemodialysis and peritoneal dialysis are the other possible options for renal replacement.
Congenital nephrotic syndrome is a rare and uniformly fatal disease which needs renal transplantation in pediatric group.

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  1. ADU D. The nephrotic syndrome: does renal biopsy affect management? Nephrol Dial Transplant [online] 1996 Jan, 11(1):12-4 [viewed 19 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/8649618
  2. COBAN M, EKE RN, KIZILATES F, UCAR S, DEDE F. Effect of steroid and cyclosporine in membranous nephropathy that is resistant to steroid and/or cytotoxic treatment. Int J Clin Exp Med [online] 2014, 7(1):255-61 [viewed 19 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24482713
  3. DAVISON AM, LAMBIE AT, VERTH AH, CASH JD. Salt-poor human albumin in management of nephrotic syndrome. Br Med J [online] 1974 Mar 16, 1(5906):481-4 [viewed 19 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/4817158
  4. DU W, ZHENG Z, HAN S, MA S, CHEN S. HBV reactivation in an occult HBV infection patient treated with prednisone for nephrotic syndrome: case report and literature review. BMC Infect Dis [online] 2013 Aug 27:394 [viewed 19 June 2014] Available from: doi:10.1186/1471-2334-13-394
  5. GIPSON D. S., MASSENGILL S. F., YAO L., NAGARAJ S., SMOYER W. E., MAHAN J. D., WIGFALL D., MILES P., POWELL L., LIN J.-J., TRACHTMAN H., GREENBAUM L. A.. Management of Childhood Onset Nephrotic Syndrome. PEDIATRICS [online] December, 124(2):747-757 [viewed 15 June 2014] Available from: doi:10.1542/peds.2008-1559
  6. GLASSOCK RJ. Attending rounds: an older patient with nephrotic syndrome. Clin J Am Soc Nephrol [online] 2012 Apr, 7(4):665-70 [viewed 19 June 2014] Available from: doi:10.2215/CJN.12771211
  7. HULL RP, GOLDSMITH DJ. Nephrotic syndrome in adults. BMJ [online] 2008 May 24, 336(7654):1185-9 [viewed 19 June 2014] Available from: doi:10.1136/bmj.39576.709711.80
  8. KANG HG. Treatment of steroid-resistant pediatric nephrotic syndrome Korean J Pediatr [online] 2011 Aug, 54(8):317-321 [viewed 20 June 2014] Available from: doi:10.3345/kjp.2011.54.8.317
  9. KERLIN BA, AYOOB R, SMOYER WE. Epidemiology and pathophysiology of nephrotic syndrome-associated thromboembolic disease. Clin J Am Soc Nephrol [online] 2012 Mar, 7(3):513-20 [viewed 19 June 2014] Available from: doi:10.2215/CJN.10131011
  10. KIM MS, PRIMACK W, HARMON WE. Congenital nephrotic syndrome: preemptive bilateral nephrectomy and dialysis before renal transplantation. J Am Soc Nephrol [online] 1992 Aug, 3(2):260-3 [viewed 20 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/1391724
  11. KODNER C. Nephrotic syndrome in adults: diagnosis and management. Am Fam Physician [online] 2009 Nov 15, 80(10):1129-34 [viewed 19 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/19904897
  12. NARITA I, FUJITA T, SHIMADA M, MURAKAMI R, SHIMAYA Y, NAKAMURA N, YAMABE H, OKUMURA K. An adult case of nephrotic syndrome presenting with pulmonary artery thrombosis: a case report. J Med Case Rep [online] 2013 Aug 23, 7(1):215 [viewed 19 June 2014] Available from: doi:10.1186/1752-1947-7-215
  13. RATHI M, BHAGAT RL, MUKHOPADHYAY P, KOHLI HS, JHA V, GUPTA KL, SAKHUJA V, JOSHI K. Changing histologic spectrum of adult nephrotic syndrome over five decades in north India: A single center experience. Indian J Nephrol [online] 2014 Mar, 24(2):86-91 [viewed 19 June 2014] Available from: doi:10.4103/0971-4065.127892
  14. SINHA A, HARI P, SHARMA PK, GULATI A, KALAIVANI M, MANTAN M, DINDA AK, SRIVASTAVA RN, BAGGA A. Disease course in steroid sensitive nephrotic syndrome. Indian Pediatr [online] 2012 Nov, 49(11):881-7 [viewed 15 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/22791676
  15. WEENING JJ. Will laboratory markers replace kidney biopsy in patients with nephrotic syndrome? Neth J Med [online] 2012 Apr, 70(3):107-8 [viewed 15 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/22516573
  16. XIA Y, MAO J, JIN X, WANG W, DU L, LIU A. Familial steroid-sensitive idiopathic nephrotic syndrome: seven cases from three families in China. Clinics (Sao Paulo) [online] 2013 May, 68(5):628-31 [viewed 19 June 2014] Available from: doi:10.6061/clinics/2013(05)08