Nephrotic Syndrome

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.

The disease is related to the following processes:  auto-immune and has an incidence of about  4 / 100.000.

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].

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.

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.

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References

  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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