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Nephrotic Syndrome

Nephrotic Syndromes

This is a nonspecific disease of the kidney characterized by proteinuria, edema and hypoalbuminemia. It results from increased permeability of the glomerulus leading to massive loss of protein in the urine.


Presentation

The commonest presenting features are those due to fluid retention. Facial edema is usually the first sign of nephrotic syndrome in children. This is followed be generalized swelling of the whole body known as anasarca. There could be ascites, pleural effusion, and pitting pedal edema. The patient could also present with frothy urine. There could be dyspnea and cough. In cases of an underlying disease, patients will present with symptoms of that disease e.g. rash in patients with lupus.

On presentation, the cardiovascular and hepatic systems should be evaluated to rule out other causes of generalized edema [7].

Pleural Effusion
  • Severe with gross limb oedema, ascites and pleural effusions.[rch.org.au]
  • When filing for Social Security Disability benefits due to a diagnosis of nephrotic syndrome, you must be able to prove that your diagnosis includes a description of how severe your edema is, including any ascites, pleural effusion or pericardial effusion[disabilitybenefitscenter.org]
  • Fluid retention may cause Dyspnea (pleural effusion or laryngeal edema) Arthralgia (hydrarthrosis) Abdominal pain (ascites or, in children, mesenteric edema) Corresponding signs may develop, including peripheral edema and ascites.[merckmanuals.com]
  • There could be ascites, pleural effusion, and pitting pedal edema. The patient could also present with frothy urine. There could be dyspnea and cough.[symptoma.com]
Weight Gain
  • Prednisone can cause increased appetite mood changes; he may be moody or irritable while taking the medicine weight gain Weigh your child as directed and record his weight. Check the urine protein once weekly or as directed.[nationwidechildrens.org]
  • gain Specific adverse reactions reported in IS clinical trials in infants and children under 2 years of age included: infection, hypertension, irritability, Cushingoid symptoms, constipation, diarrhea, vomiting, pyrexia, weight gain, increased appetite[actharnephrology.com]
  • Symptoms may include: Fatigue and malaise Decreased appetite Weight gain and facial swelling Abdominal swelling or pain Foamy urine Fluid accumulation in the body spaces (edema) Pale fingernail beds Dull hair Ears cartilage may feel less firm Food intolerances[stanfordchildrens.org]
Fatigue
  • […] alternates between strong craving for food and aversion to food; characterized by excessive eating followed by periods of fasting or self-induced vomiting Lambert-Eaton syndrome a disease seen in patients with lung cancer and characterized by weakness and fatigue[vocabulary.com]
  • Symptoms may include: Fatigue and malaise Decreased appetite Weight gain and facial swelling Abdominal swelling or pain Foamy urine Fluid accumulation in the body spaces (edema) Pale fingernail beds Dull hair Ears cartilage may feel less firm Food intolerances[stanfordchildrens.org]
  • Fatigue. Weight gain (from fluid buildup). Foam when urinating. Loss of appetite. How is nephrotic syndrome diagnosed? Doctors diagnose nephrotic syndrome using: Urine tests to measure the amount of protein in your urine.[uwhealth.org]
Weakness
  • […] person alternates between strong craving for food and aversion to food; characterized by excessive eating followed by periods of fasting or self-induced vomiting Lambert-Eaton syndrome a disease seen in patients with lung cancer and characterized by weakness[vocabulary.com]
  • The patient feels increasingly weak and fatigued. Appetite is greatly decreased. Over time, the loss of protein causes the muscles to become weak and small (called muscle wasting). The patient may note abdominal pain and difficulty breathing.[encyclopedia.com]
  • Fc gamma receptors might modulate response to rituximab; since 60 of the enrolled patients were treated with rituximab, we also tested the association between the studied SNPs and rituximab efficacy in this patient subgroup, but found only a weak association[ncbi.nlm.nih.gov]
Malaise
  • Symptoms may include: Fatigue and malaise Decreased appetite Weight gain and facial swelling Abdominal swelling or pain Foamy urine Fluid accumulation in the body spaces (edema) Pale fingernail beds Dull hair Ears cartilage may feel less firm Food intolerances[stanfordchildrens.org]
  • Cough and difficulty in breathing as well as a general feeling of malaise. Diagnosis: This is usually done by urine investigations to check the amount and type of protein in urine. Blood tests could also be done to check for renal function.[symptoma.com]
  • Symptoms of nephrotic syndrome The symptoms of nephrotic syndrome include: foamy and frothy urine unexplained weight loss general malaise (feeling unwell) oedema (fluid retention or swelling), particularly around the abdomen (belly area), legs and eyes[betterhealth.vic.gov.au]
Leg Swelling
  • Protein loss causes low protein count in the blood (hypoalbuminemia) and edemas (excess fluid in the interstitial cavity which is between the cells, causes leg swelling most often, and also in the adbomen and around the eyes).[medical-dictionary.thefreedictionary.com]
Abdominal Pain
  • History can also include weight gain, poor urine output, dizziness, or discomfort as a result of the oedema (including abdominal pain).[rch.org.au]
  • The patient may note abdominal pain and difficulty breathing. Because the kidneys are involved in blood pressure regulation, abnormally low or abnormally high blood pressure may develop.[encyclopedia.com]
  • Think of spontaneous bacterial peritonitis in patient with fever and abdominal pain. Thromboembolic Events 2-9% of children with nephrotic syndrome will develop clots. Imbalance between anticoagulants and procoagulants.[pedemmorsels.com]
  • pain,persistent vomiting,dizziness and cold extremities 19.[slideshare.net]
  • Call your child’s healthcare provider if your child has: Symptoms that don’t get better, or get worse New symptoms Nausea or vomiting, or abdominal pain Unexpected weight gain or swelling in the legs, ankles, or around the eyes Dark colored urine Less[urmc.rochester.edu]
Loss of Appetite
  • Loss of appetite. How is nephrotic syndrome diagnosed? Doctors diagnose nephrotic syndrome using: Urine tests to measure the amount of protein in your urine.[uwhealth.org]
  • Signs and symptoms Signs and symptoms include: Foamy urine Fatigue and weakness Swelling, especially around the eyes, hands, feet, and abdomen Loss of appetite Increased weight from fluid retention High protein levels in the urine and low protein levels[southerncross.co.nz]
  • […] of appetite When to see a doctor Make an appointment with your doctor if you have any signs or symptoms that worry you.[mayoclinic.org]
Abdominal Distension
  • In addition, a careful history should exclude possible complications and identify children with atypical presentations that might reflect other serious systemic illnesses. 39 It should include an evaluation of any abdominal distension, which is usually[slideplayer.com]
Hypertension
  • Persistent hypertension (can have mild hypertension first 1-2 days) Rule out any nephritic features (requiring entirely different management) Macroscopic haematuria (INS may have microscopic haematuria) Hypertension Raised serum creatinine (INS may have[rch.org.au]
  • As mentioned previously, the nephritic syndrome ischaracterized by haematuria (which is absent in nephrotic syndrome) as well asuraemia, hypertension, proteinuria and oliguria.[newhealthadvisor.com]
  • Treatment with Acthar was well tolerated; one patient had an early termination of treatment due to weight gain and hypertension.[prnewswire.com]
  • Prior to admission, the level of proteinuria on successive check-ups was over 3.5 g day, while on treatment with Losartan for the past six months for mild arterial hypertension.[ncbi.nlm.nih.gov]
  • […] infections are suspected in infants Acthar is contraindicated in patients with scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of or the presence of a peptic ulcer, congestive heart failure, uncontrolled hypertension[actharnephrology.com]
Orthostatic Hypotension
  • hypotension). loss of appetite fatigue Causes of nephrotic syndrome Some of the causes of nephrotic syndrome include: changes to the immune system (minimal change disease or lipoid nephrosis) – nephrotic syndrome due to changes to the immune system is[betterhealth.vic.gov.au]
Facial Swelling
  • Symptoms may include: Fatigue and malaise Decreased appetite Weight gain and facial swelling Abdominal swelling or pain Foamy urine Fluid accumulation in the body spaces (edema) Pale fingernail beds Dull hair Ears cartilage may feel less firm Food intolerances[stanfordchildrens.org]
  • It may occur: In the face and around the eyes ( facial swelling ) In the arms and legs, especially in the feet and ankles In the belly area ( swollen abdomen ) Other symptoms include: Foamy appearance of the urine Poor appetite Weight gain (unintentional[nicklauschildrens.org]
  • Organ edema (ascites, pulmonary effusion, facial swelling and lower extremities) and anasarca Loss of albumin through the glomeruli leads to a significant drop in oncotic pressure at the venular end of the vascular beds, causing fluid accumulation in[pathophys.org]
Facial Edema
  • Facial edema is usually the first sign of nephrotic syndrome in children. This is followed be generalized swelling of the whole body known as anasarca. There could be ascites, pleural effusion, and pitting pedal edema.[symptoma.com]
Oliguria
  • As mentioned previously, the nephritic syndrome ischaracterized by haematuria (which is absent in nephrotic syndrome) as well asuraemia, hypertension, proteinuria and oliguria.[newhealthadvisor.com]
  • […] proteinuria ( 3g/day), edema, hypoalbuminemia, hyperlipidemia, and lipiduria (can be localized kidney process or as part of a systemic disease) vs. nephritic syndrome: hematuria, oliguria, hypertension, and renal insufficiency (almost always immune mediated[errolozdalga.com]
  • The signs include cold hands and feet, delayed capillary filling, oliguria, and tachycardia. Hypotension is a late feature.[emedicine.medscape.com]
  • CONGENITAL NEPHROTIC SYNDROME • Presents in first 3 months of life Etiology:heterogenous Finnish form –NPHS1 mutation, AR NPHS2,PLCE 1 mutation intrauterine infections CLINICAL FEATURES: anasarca,hypoalbuminaemia,oliguria HISTOLOGY: microcystic dilatation[slideshare.net]
Headache
  • […] vomiting Lambert-Eaton syndrome a disease seen in patients with lung cancer and characterized by weakness and fatigue of hip and thigh muscles and an aching back; caused by antibodies directed against the neuromuscular junctions Chinese restaurant syndrome headache[vocabulary.com]
  • , including swelling in face, belly, or arms and legs, or skin sores You're being treated for nephrotic syndrome, but your symptoms don't improve New symptoms develop, including cough, decreased urine output, discomfort with urination, fever, severe headache[nlm.nih.gov]
  • Contact a Medical Professional Call your health care provider if: You have symptoms of nephrotic syndrome Nephrotic syndrome does not go away New symptoms develop, including cough , decreased urine output , discomfort with urination , fever , severe headache[nicklauschildrens.org]

Workup

  • Laboratory investigations are the mainstay of diagnosis and they center on urine investigations. The first test should be urinalysis, 3 or 4 pluses of urine on the dipstick corresponds to at least 3g/L of protein and this is well within the nephrotic syndrome range. The presence of glucose should prompt further investigation of diabetes.
  • Urine sediment examination under a microscope with show waxy cast which indicates a proteinuric disease. It will also show red blood cells which indicates glomerular disease [8].
  • Measurement of 24-hour protein will reveal > 150mg of protein which is more than normal for a healthy kidney. Urine protein electrophoresis will show the exact protein and proteinuria without albumin may rule our nephrotic syndrome.
  • Serum electrolyte, urea and creatinine should also be checked to determine renal function.
  • A renal ultrasound can also be done and high echogenicity of the kidney is a pointer to chronic kidney disease. It will also show if a patient has one or two kidneys. One kidney is a contraindication for renal biopsy which may be done if the nephrotic syndrome is of unknown origin.
Hyponatremia
  • Identify the cause of hyponatremia in nephrotic syndrome. Recognize complications associated with nephrotic syndrome, including those resulting from diuretic therapy. Understand the various factors that affect the prognosis of nephrotic syndrome.[pedsinreview.aappublications.org]
  • Hyponatremia also occurs with a low fractional sodium excretion . Hyperlipidaemia is caused by two factors: Hypoproteinemia stimulates protein synthesis in the liver, resulting in the overproduction of lipoproteins .[en.wikipedia.org]
  • Hyponatremia and hyperkalemia can be seen, with hyperkalemia developing in patients who are oliguric. Serum C3 levels are normal in cases of minimal change disease.[hawaii.edu]
Globulins Increased
  • Lab Increased alpha2-globulin, increased beta-globulin, decreased albumin, increased cholesterol, increased TGs, increased phospholipids; these increases are confined to lipoproteins containing apoB (chylomicrons and LDL-C), due to increased production[medical-dictionary.thefreedictionary.com]
Beta Globulin Decreased
  • Lab Increased alpha2-globulin, increased beta-globulin, decreased albumin, increased cholesterol, increased TGs, increased phospholipids; these increases are confined to lipoproteins containing apoB (chylomicrons and LDL-C), due to increased production[medical-dictionary.thefreedictionary.com]
Hypertriglyceridemia
  • Patients have increased LDL, increased lipoproteins, and hypertriglyceridemia . Anemia Transferrin and Erythropoietin are lost. Both can lead to microcytic anemia. Low 25-hydroxy-Vitamin D levels Loss of Vitamin D binding protein.[pedemmorsels.com]
Pleural Effusion
  • Severe with gross limb oedema, ascites and pleural effusions.[rch.org.au]
  • When filing for Social Security Disability benefits due to a diagnosis of nephrotic syndrome, you must be able to prove that your diagnosis includes a description of how severe your edema is, including any ascites, pleural effusion or pericardial effusion[disabilitybenefitscenter.org]
  • Fluid retention may cause Dyspnea (pleural effusion or laryngeal edema) Arthralgia (hydrarthrosis) Abdominal pain (ascites or, in children, mesenteric edema) Corresponding signs may develop, including peripheral edema and ascites.[merckmanuals.com]
  • There could be ascites, pleural effusion, and pitting pedal edema. The patient could also present with frothy urine. There could be dyspnea and cough.[symptoma.com]

Treatment

  • The treatment of nephrotic syndrome is directed at the specific cause of the disease.
  • In minimal change nephropathy, glucocorticoids are used. Children who do not respond to glucocorticoid treatment should be given rituximab. Rituximab also has application in the treatment of adult membranous nephropathy [9].
  • Anti-inflammatory treatment is used in amyloidosis and cyclophosphamide along with prednisone for lupus.
  • In patients with membranous nephropathy who have a low risk of progression, expectant management without immunosuppression can be employed.
  • Diuretics are used to control edema, antibiotics for infections, anticoagulation therapy to decrease risk of clots and the diet should be rich in protein and calories.

Prognosis

Treatment greatly reduces the morbidity and mortality associated with this condition. The prognosis is however dependent on the cause of the nephrotic syndrome. It is poor in infants with congenital nephrotic syndrome as they hardly survive beyond months. The best prognosis is in patients with minimal change nephropathy. Mesangiocapillary glomerulonephrits carries the worst prognosis and patients develop renal failure within 3 years. Without treatment, this condition carries a very bad prognosis especially in adults over 30 years [6].

Etiology

The causes of nephrotic syndrome are primary when it is due to a specific disease or secondary when it is an exhibition of a systemic illness.

Primary causes of nephrotic syndrome include; Minimal change nephropathy, focal segmental glomerulosclerosis, rapidly progressing glomerulonephritis, membranous glomerulonephritis and mesangial proliferating glomerulonephritis.

Secondary causes are; Diabetes mellitus causing diabetic nephropathy, systemic lupus erythematosus, sarcoidosis, preeclampsia, viral illnesses like hepatitis C, hepatitis B and HIV, amyloidosis, other infections like syphilis, multiple myeloma, vasculitis, genetic disorders and drugs [2].

Epidemiology

In adults, the main cause is diabetic nephropathy which presents mainly as mesangiocapillary glomerulonephritis. While in children, the most frequent glomerulopathy is minimal change disease. Overall, diabetic nephropathy is the most common cause of this disease with an estimated 50 cases per million population.African Americans, American Indians and Hispanics have a higher incidence which is attributable to the incidence of diabetes amongst these races. It generally affects more men than women although lupus nephritis is common in women. It affects more adult than children with an estimated adult:child ratio of 26:1. The peak period of incidence is between 40 – 50 years [3].

Sex distribution
Age distribution

Pathophysiology

The glomerulus is responsible for filtration in the kidney. In normal healthy individuals, the amount of protein filtered through the glomerulus is less than 0.1%. In nephrotic syndrome, there is destruction of the glomerular structure as it destructs the endothelial surface, glomerular basement membrane or the podocytes. This will lead to an increase in glomerular permeability that leads to loss of albumin in the urine. The loss of albumin, which is the major protein responsible for maintaining the plasma colloid osmotic pressure, will lead to a drop in the pressure. This drop in plasma oncotic pressure will lead to greater filtration of water at the capillaries throughout the body leading to edema. Eventually, as the damage worsens, bigger proteins like the immunoglobulins are also lost in urine [4].

The metabolic effects of proteinuria are far reaching and include infections due to loss of immunoglobulins, hyperlipidemia secondary to the liver's attempt to compensate for protein loss by synthesizing lipoproteins. Other effects are hypocalcemia, hypercoagulability, and hypovolemia [5].

Prevention

In patients who are risk of developing this condition and have mild proteinuria, the use of Angiotensin converting enzyme inhibitors like elanapril has been shown to prevent worsening of proteinuria and kidney function. Also, treating infections that may cause it and preventing risk factors are known preventive measures [10].

Summary

Nephrotic syndrome is when there is proteinuria of over 3 grams daily or 2 grams of protein per gram of creatinine. It has a number of causes and water retention is a major component. Primary or secondary damage to the glomeruli alters their capacity to filter protein leading to the massive loss of protein [1].

Patient Information

Definition: Nephrotic syndrome is the presence of protein in the urine. It is characterized by an increase loss of protein due to damage to the filtering mechanisms in the kidney. In normal individuals, there is very little protein loss in urine

Cause: It is caused by factors that either damage the filtration apparatus directly or as a result of another disease like diabetes causing the damage. It is also caused by infections and certain drug use.

Symptoms: The early symptoms are facial puffiness which is usually worse in the morning. The may be leg and abdominal swelling and generalized swelling of the whole body. The urine could also be unusually foamy. Cough and difficulty in breathing as well as a general feeling of malaise.

Diagnosis: This is usually done by urine investigations to check the amount and type of protein in urine. Blood tests could also be done to check for renal function. Ultrasound is also done to check the structure of the kidneys.

Treatment: Treatment is directed at the cause of the disease. Drugs are also given to reduce the fluid level and to treat infections. Most children require steroid treatment.

References

Article

  1. Vaziri ND. Endocrinological consequences of the nephrotic syndrome. Am J Nephrol 1993; 13:360.
  2. MacDonald NE, Wolfish N, McLaine P, et al. Role of respiratory viruses in exacerbations of primary nephrotic syndrome. J Pediatr 1986; 108:378.
  3. Kerlin BA, Ayoob R, Smoyer WE. Epidemiology and pathophysiology of nephrotic syndrome-associated thromboembolic disease. Clin J Am Soc Nephrol. Mar 2012;7(3):513-20
  4. [Guideline] International Study of Kidney Disease in Children (ISKDC). Nephrotic syndrome in children: prediction of histopathology from clinical and laboratory characteristics at time of diagnosis. A report of the International Study of Kidney Disease in Children. Kidney Int. Feb 1978;13(2):159-65.
  5. Tryggvason K, Patrakka J, Wartiovaara J. Hereditary proteinuria syndromes and mechanisms of proteinuria.N Engl J Med. Mar 30 2006;354(13):1387-401.
  6. YAMAUCHI H, HOPPER J Jr. HYPOVOLEMIC SHOCK AND HYPOTENSION AS A COMPLICATION IN THE NEPHROTIC SYNDROME. REPORT OF TEN CASES. Ann Intern Med 1964; 60:242.
  7. White RH, Glasgow EF, Mills RJ. Clinicopathological study of nephrotic syndrome in childhood. Lancet 1970; 1:1353.
  8. Howard AD, Moore J Jr, Gouge SF, et al. Routine serologic tests in the differential diagnosis of the adult nephrotic syndrome. Am J Kidney Dis 1990; 15:24.
  9. Kamei K, Ito S, Nozu K, et al. Single dose of rituximab for refractory steroid-dependent nephrotic syndrome in children. Pediatr Nephrol. Jul 2009;24(7):1321-8.
  10. Bonilla-Felix M, Parra C, Dajani T, et al. Changing patterns in the histopathology of idiopathic nephrotic syndrome in children. Kidney Int 1999; 55:1885.

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