eMedicine Specialties > Nephrology > Glomerular Diseases

Nephrotic Syndrome

Author: Eric P Cohen, MD, Professor of Medicine, Nephrology Fellowship Program Director, Department of Medicine, Division of Nephrology, Medical College of Wisconsin; Nephrology Section Chief, Zablocki Veterans Affairs Hospital
Contributor Information and Disclosures

Updated: Aug 25, 2009

Introduction

Background

Nephrotic syndrome is kidney disease with proteinuria, hypoalbuminemia, and edema. Nephrotic range proteinuria is 3 grams per day or more. On a single, "spot" urine collection, it is 2 grams of protein per gram of urine creatinine.

There are many specific causes of nephrotic syndrome. These include kidney diseases such as minimal-change nephropathy, focal glomerulosclerosis, and membranous nephropathy. Nephrotic syndrome can also result from systemic diseases that affect other organs in addition to the kidneys, such as diabetes, amyloidosis, and lupus erythematosus. A schematic drawing of the glomerular barrier is shown below.

Schematic drawing of the glomerular barrier. Podo...

Schematic drawing of the glomerular barrier. Podo = podocytes; GBM = glomerular basement membrane; Endo = fenestrated endothelial cells; ESL = endothelial cell surface layer (often referred to as the glycocalyx). Primary urine is formed through the filtration of plasma fluid across the glomerular barrier (arrows); in humans, the glomerular filtration rate (GFR) is 125 mL/min. The plasma flow rate (Qp) is close to 700 mL/min, with the filtration fraction being 20%. The concentration of albumin in serum is 40 g/L, while the estimated concentration of albumin in primary urine is 4 mg/L, or 0.1% of its concentration in plasma. Reproduced from Haraldsson et al, Physiol Rev 88: 451-487, 2008, and by permission of the American Physiological Society (www.the-aps.org).

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Schematic drawing of the glomerular barrier. Podo...

Schematic drawing of the glomerular barrier. Podo = podocytes; GBM = glomerular basement membrane; Endo = fenestrated endothelial cells; ESL = endothelial cell surface layer (often referred to as the glycocalyx). Primary urine is formed through the filtration of plasma fluid across the glomerular barrier (arrows); in humans, the glomerular filtration rate (GFR) is 125 mL/min. The plasma flow rate (Qp) is close to 700 mL/min, with the filtration fraction being 20%. The concentration of albumin in serum is 40 g/L, while the estimated concentration of albumin in primary urine is 4 mg/L, or 0.1% of its concentration in plasma. Reproduced from Haraldsson et al, Physiol Rev 88: 451-487, 2008, and by permission of the American Physiological Society (www.the-aps.org).


Nephrotic syndrome may affect adults and children, of both sexes and of any race. It may occur in typical form, or in association with nephritic syndrome. The latter connotes glomerular inflammation, with hematuria and impaired kidney function.

[#target1] Classification

Nephrotic syndrome can be primary, being a disease specific to the kidneys, or it can be secondary, being a renal manifestation of a systemic general illness. In all cases, injury to glomeruli is an essential feature.

Primary causes of nephrotic syndrome include, in approximate order of frequency:

  • Minimal-change nephropathy
  • Focal glomerulosclerosis
  • Membranous nephropathy
  • Hereditary nephropathies

Secondary causes include, again in order of approximate frequency:

  • Diabetes mellitus
  • Lupus erythematosus
  • Amyloidosis and paraproteinemias
  • Viral infections (eg, hepatitis B, hepatitis C, human immunodeficiency virus [HIV] )
  • Preeclampsia

Nephrotic-range proteinuria may occur in other kidney diseases, such as IgA nephropathy. In that common glomerular disease, one third of subjects may have nephrotic-range proteinuria.1 Nephrotic syndrome may occur in persons with sickle cell disease and evolve to renal failure. Membranous nephropathy may complicate bone marrow transplantation, in association with graft versus host disease. Kidney diseases that affect tubules and interstitium, such as interstitial nephritis, will not cause nephrotic syndrome.

The above causes of nephrotic syndrome are largely those for adults, and this article will concentrate primarily on adult nephrotic syndrome.

However, nephrotic syndrome in infancy and childhood is an important entity. A study from New Zealand found the incidence of nephrotic syndrome to be almost 20 cases per million children under age 15 years.2 In specific populations, such as those of Finnish or Mennonite origin, congenital nephrotic syndrome may occur in 1 in 10,000 or 1 in 500 births, respectively.3 According to the International Study of Kidney Diseases in Childhood (ISKDC), 84.5% of all children with primary nephrotic syndrome have minimal-change nephrotic syndrome (MCNS), 9.5% have focal segmental glomerulosclerosis (FSGS), 2.5% have mesangial proliferation, and 3.5% have membranous nephropathy or another cause of the disease.4,5 Increasing trends of FSGS incidence are being reported, but MCNS remains the most important cause of chronic renal disease in children.

From a therapeutic perspective, nephrotic syndrome may be classified as steroid sensitive, steroid resistant, steroid dependent, or frequently relapsing.

Pathophysiology

Glomerular permeability

In a healthy individual, less than 0.1% of plasma albumin may traverse the glomerular filtration barrier.6 Controversy exists regarding the sieving of albumin across the glomerular permeability barrier. Specifically, it is proposed that there is ongoing albumin passage into the urine, in many grams per day, with equivalent substantial tubular uptake of albumin, the result being that the urine has 80 mg per day or less of daily albumin.7 This controversy is based on studies in experimental animals. However, studies of humans with tubular transport defects suggest that the glomerular urinary space albumin concentration is 3.5 mg/L.8 With this concentration, and a normal daily glomerular filtration rate (GFR) of 150 liters, one would expect no more than 525 mg per day of albumin in the final urine. Amounts above that level point to glomerular disease.

The glomerular capillaries are lined by a fenestrated endothelium that sits on the glomerular basement membrane, which in turn is covered by glomerular epithelium, or podocytes, which envelops the capillaries with cellular extensions called foot processes. In between the foot processes are the filtration slits. These 3 structures—the fenestrated endothelium, glomerular basement membrane, and glomerular epithelium—are the glomerular filtration barrier. A schematic drawing of the glomerular barrier is seen in the image below.

Schematic drawing of the glomerular barrier. Podo...

Schematic drawing of the glomerular barrier. Podo = podocytes; GBM = glomerular basement membrane; Endo = fenestrated endothelial cells; ESL = endothelial cell surface layer (often referred to as the glycocalyx). Primary urine is formed through the filtration of plasma fluid across the glomerular barrier (arrows); in humans, the glomerular filtration rate (GFR) is 125 mL/min. The plasma flow rate (Qp) is close to 700 mL/min, with the filtration fraction being 20%. The concentration of albumin in serum is 40 g/L, while the estimated concentration of albumin in primary urine is 4 mg/L, or 0.1% of its concentration in plasma. Reproduced from Haraldsson et al, Physiol Rev 88: 451-487, 2008, and by permission of the American Physiological Society (www.the-aps.org).

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Schematic drawing of the glomerular barrier. Podo...

Schematic drawing of the glomerular barrier. Podo = podocytes; GBM = glomerular basement membrane; Endo = fenestrated endothelial cells; ESL = endothelial cell surface layer (often referred to as the glycocalyx). Primary urine is formed through the filtration of plasma fluid across the glomerular barrier (arrows); in humans, the glomerular filtration rate (GFR) is 125 mL/min. The plasma flow rate (Qp) is close to 700 mL/min, with the filtration fraction being 20%. The concentration of albumin in serum is 40 g/L, while the estimated concentration of albumin in primary urine is 4 mg/L, or 0.1% of its concentration in plasma. Reproduced from Haraldsson et al, Physiol Rev 88: 451-487, 2008, and by permission of the American Physiological Society (www.the-aps.org).


Filtration of plasma water and solutes is extracellular and occurs through the endothelial fenestrae and filtration slits. The importance of the podocytes and the filtration slits is shown by genetic diseases. Thus, in congenital nephrotic syndrome of the Finnish type, the gene for nephrin, a protein of the filtration slit, is mutated, leading to nephrotic syndrome in infancy . Similarly, podocin, a protein of the podocytes, may be abnormal in a number of children with steroid-resistant focal glomerulosclerosis.

The glomerular structural changes that may cause proteinuria are (1) damage to the endothelial surface, (2) damage to the glomerular basement membrane, and/or (3) damage of the podocytes. One or more of these mechanisms may be seen in any one type of nephrotic syndrome. Albuminuria alone may occur, or, with greater injury, leakage of all plasma proteins, (ie, proteinuria) may take place.

Proteinuria that is more than 85% albumin is selective proteinuria. Albumin has a net negative charge, and it is proposed that loss of glomerular membrane negative charges could be important in causing albuminuria. Nonselective proteinuria, being a glomerular leakage of all plasma proteins, would not involve changes in glomerular net charge but rather a generalized defect in permeability. This construct does not permit clear-cut separation of causes of proteinuria, except in minimal-change nephropathy, in which proteinuria is selective.

Pathogenesis of edema

An increase in glomerular permeability leads to albuminuria and eventually to hypoalbuminemia. In turn, hypoalbuminemia lowers the plasma colloid osmotic pressure, causing greater transcapillary filtration of water throughout the body and thus the development of edema.

Capillary hydrostatic pressure and the gradient of plasma to interstitial fluid oncotic pressure determine the movement of fluid from the vascular compartment to the interstitium. The oncotic pressure is mainly determined by the protein content. The flux of water across the capillary wall can be expressed by the following formula:

Qw = K ([Pc - Pi] - [pp - pi]

In this formula, Qw is net flux of water, K is the capillary filtration coefficient, Pc is capillary hydrostatic pressure, and Pi is the interstitial fluid hydrostatic pressure, while pp is the plasma oncotic pressure, and pi is the interstitial fluid oncotic pressure. With a high enough capillary hydrostatic pressure or a low enough intravascular oncotic pressure, the amount of fluid filtered exceeds the maximal lymphatic flow, and edema occurs. In patients with nephrotic syndrome, this causes a reduction in plasma volume, with a secondary increase of sodium and water retention by the kidneys.

An alternate hypothesis is that a condition of renal sodium retention occurs because of the proteinuria, but this is not related to intravascular volume or to serum protein concentration. The evidence supporting this hypothesis includes the fact that (1) sodium retention is observed even before the serum albumin level starts falling and (2) intravascular volume is normal or even increased in most patients with nephrotic syndrome. This could occur if intraluminal protein directly stimulated renal epithelial sodium reabsorption.9

A third possible mechanism is an enhanced peripheral capillary permeability to albumin, as shown by radioisotopic technique in human studies of 60 patients with nephrotic syndrome.10 This would then lead to increased tissue oncotic pressure and fluid retention in the peripheral tissues.

Metabolic consequences of proteinuria

In the nephrotic syndrome, levels of serum lipids are usually elevated. This can occur via (1) hypoproteinemia that stimulates protein, including lipoprotein, synthesis by the liver, and (2) diminution of lipid catabolism caused by reduced plasma levels of lipoprotein lipase.

The loss of antithrombin III and plasminogen via urine, along with the simultaneous increase in clotting factors, especially factors I, VII, VIII, and X, increases the risk for venous thrombosis and pulmonary embolism. In the first 6 months that a patient has nephrotic syndrome, the occurrence rate of venous thrombosis may reach 10%.11

Vitamin D–binding protein may be lost in the urine, leading to hypovitaminosis D, with malabsorption of calcium and development of bone disease.12

Urinary immunoglobulin losses may lower the patient's resistance to infections and increase the risk of sepsis and peritonitis.

Frequency

United States

The figure below shows the incidence per million population of important causes of nephrotic syndrome. Diabetic nephropathy with nephrotic syndrome is most common, at an estimated rate of at least 50 cases per million population. That is an underestimation, however, since the rate of end-stage renal disease from diabetes has reached 100 cases per million population in some Western countries. In children, nephrotic syndrome may occur at a rate of 20 cases per million children.2

Incidence of important causes of nephrotic syndro...

Incidence of important causes of nephrotic syndrome, in number per million population. The left panel shows systemic causes, and the right panel lists primary renal diseases that can cause nephrotic syndrome. fgs = focal glomerulosclerosis, MN = membranous nephropathy, min change = minimal-change nephropathy. Data are in part from Swaminathan et al and Bergesio et al.

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Incidence of important causes of nephrotic syndro...

Incidence of important causes of nephrotic syndrome, in number per million population. The left panel shows systemic causes, and the right panel lists primary renal diseases that can cause nephrotic syndrome. fgs = focal glomerulosclerosis, MN = membranous nephropathy, min change = minimal-change nephropathy. Data are in part from Swaminathan et al and Bergesio et al.


International

Biopsy studies in children with nephrotic syndrome have shown similar types of histology in India and Turkey, compared with what one would expect in Western countries.13,14 In Pakistani adults with nephrotic syndrome, the spectrum of histologies of kidney biopsies has been found to be similar to that seen in western countries.15

Glomerular disease may be associated with schistosomal infection, as could occur in Egypt.16

So-called "tropical nephrotic syndrome" may not be a true entity. Doe et al summarized the evidence for causes of nephrotic syndrome in African children.17 All of the typical histologies may be found on kidney biopsy. The connection of nephrotic syndrome to quartan malaria is not well-established. Indeed, Pakasa and Sumaili call attention to the apparent decline of parasite-associated nephrotic syndrome in the Congo.18,19 It is possible that the perceived association between nephrotic syndrome and parasitic infections was coincidental, as supported by the ongoing and probably increasing occurrence of chronic kidney disease in the Congo.19

Mortality/Morbidity

  • In the preantibiotic era, infection was a major factor in the mortality rate among patients with nephrotic syndrome.20 Treatments for nephrotic syndrome and its complications appear to have reduced the morbidity and mortality once associated with the syndrome.
  • A study by Donadio et al of 140 patients with idiopathic membranous nephropathy, 89 of whom received no treatment with corticosteroids or immunosuppressive drugs and 51 of whom were treated primarily with short-term courses of prednisone alone, found that the patients' survival rates were  the same as those expected for the general population.21 This supports the clinical practice of expectant management for the first 6 months, without immunosuppression, in persons with membranous nephropathy and a low risk for progression.22
  • The prognosis may worsen because of (1) an increased incidence of renal failure and the complications secondary to nephrotic syndrome, including thrombotic episodes and infection, or (2) treatment-related conditions, such as infectious complications of immunosuppressive treatments.
  • In secondary nephrotic syndromes, morbidity and mortality are related to the primary disease process, such as diabetes or lupus, although in diabetic nephropathy, the magnitude of proteinuria itself relates directly to mortality.23

Race

  • Because diabetes is major cause of nephrotic syndrome, American Indians, Hispanics, and African Americans have a higher incidence of nephrotic syndrome than do white persons.
  • HIV nephropathy is a complication of HIV that is unusual in whites; it is seen with greater frequency in African Americans.24
  • Focal glomerulosclerosis appears to be overrepresented in African American children, as compared with white children, as a cause of nephrotic syndrome.25

Sex

  • There is a male predominance in the occurrence of nephrotic syndrome, as there is for chronic kidney disease in general. This male overrepresentation is also seen in paraneoplastic membranous nephropathy.26
  • However, lupus nephritis affects mostly women.

Age

The image below shows typical ages at which a given cause of nephrotic syndrome may occur. It does not show every possible cause of nephrotic syndrome, such as lupus nephritis, which typically affects young black women. The ages shown are averages.

A schema of the average patient ages associated w...

A schema of the average patient ages associated with various common forms of nephrotic syndrome.

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A schema of the average patient ages associated w...

A schema of the average patient ages associated with various common forms of nephrotic syndrome.


Clinical

History

  • The first sign of nephrotic syndrome in children is usually swelling of the face; this is followed by swelling of the entire body.
  • Adults can present with dependent edema.
  • Foamy urine may be a presenting feature.
  • A thrombotic complication, such as deep vein thrombosis of the calf veins or even a pulmonary embolus, may be the first clue indicating nephrotic syndrome.
  • Additional historical features that appear can be related to the cause of nephrotic syndrome. Thus, the recent start of a nonsteroidal anti-inflammatory drug (NSAID) or a 10-year history of diabetes may be very relevant.

Physical

  • Edema is the predominant feature of nephrotic syndrome and initially develops around the eyes and legs. With time, the edema becomes generalized and may be associated with an increase in weight, the development of ascites, or pleural effusions.
  • Hematuria and hypertension manifest in a minority of patients.
  • Additional features on exam will vary according to cause and as a result of whether or not renal function impairment exists. Thus, in the case of longstanding diabetes, there may be diabetic retinopathy, which correlates closely with diabetic nephropathy. If the kidney function is reduced, there may be hypertension and/or anemia.

Causes

  • The usual causes of nephrotic syndrome are discussed above (see Background). They include primary kidney diseases, such as minimal-change nephropathy, membranous nephropathy, and focal glomerulosclerosis, as well as systemic diseases, such as diabetes mellitus, lupus erythematosus, and amyloidosis.
  • Congenital and hereditary focal glomerulosclerosis may result from mutations of genes that code for podocyte proteins, including nephrin, podocin, or the cation channel 6 protein.
  • Nephrotic syndrome can result from drugs of abuse, such as heroin.
  • Nephrotic-range proteinuria occurring in the third trimester of pregnancy is the classical finding of preeclampsia. In that condition, also known as toxemia, there is hypertension as well. It may occur de novo or it may be superimposed on another chronic kidney disease. In the latter case, there will have been preexisting proteinuria that will have worsened during pregnancy.
  • Medication can cause nephrotic syndrome. This includes the very infrequent occurrence of minimal-change nephropathy with NSAID use, and the occurrence of membranous nephropathy with the administration of gold and penicillamine, which are older drugs used for rheumatic diseases; there have also been reports of focal glomerulosclerosis in association with bisphosphonates. Although recognized, these associations have not yet been quantified.
  • Nephrotic-range proteinuria could occur with the use of anticancer agents, such as bevacizumab, that inhibit vascular endothelial growth factor (VEGF).27 However, the clinical picture of this complication is of a thrombotic microangiopathy rather than of nephrotic syndrome per se.
  • The association of membranous nephropathy with cancer is a clinical dilemma. This association presumably results from immune complex injury to the glomerulus caused by cancer antigens.

    While there are about 6000 new cases of membranous nephropathy per year in the United States, there are 1.5 million new cases of nonskin cancer. Therefore, from the oncologist’s standpoint, the problem of paraneoplastic membranous nephropathy is trivial. Nonetheless, a carefully performed analysis from France suggested that the cancer rate in persons with membranous nephropathy is approximately 10-fold higher than it is in the general population, especially in individuals over age 65 years.26 In that study, 50% of membranous nephropathy cases were diagnosed before the diagnosis of cancer. Thus, in some subjects with membranous nephropathy, one should consider the possibility of an undiagnosed cancer.

More on Nephrotic Syndrome

Overview: Nephrotic Syndrome
Differential Diagnoses & Workup: Nephrotic Syndrome
Treatment & Medication: Nephrotic Syndrome
Follow-up: Nephrotic Syndrome
Multimedia: Nephrotic Syndrome
References
Further Reading
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References

  1. Neelakantappa K, Gallo GR, Baldwin DS. Proteinuria in IgA nephropathy. Kidney Int. Mar 1988;33(3):716-21. [Medline].

  2. Wong W. Idiopathic nephrotic syndrome in New Zealand children, demographic, clinical features, initial management and outcome after twelve-month follow-up: results of a three-year national surveillance study. J Paediatr Child Health. May 2007;43(5):337-41. [Medline].

  3. Niaudet P. Genetic forms of nephrotic syndrome. Pediatr Nephrol. Dec 2004;19(12):1313-8. [Medline].

  4. International Study of Kidney Disease in Children. Primary nephrotic syndrome in children: clinical significance of histopathologic variants of minimal change and of diffuse mesangial hypercellularity. A Report of the International Study of Kidney Disease in Children. Kidney Int. Dec 1981;20(6):765-71. [Medline].

  5. International Study of Kidney Disease in Children. The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. J Pediatr. Apr 1981;98(4):561-4. [Medline].

  6. Haraldsson B, Nyström J, Deen WM. Properties of the glomerular barrier and mechanisms of proteinuria. Physiol Rev. Apr 2008;88(2):451-87. [Medline].

  7. Russo LM, Bakris GL, Comper WD. Renal handling of albumin: a critical review of basic concepts and perspective. Am J Kidney Dis. May 2002;39(5):899-919. [Medline].

  8. Norden AG, Lapsley M, Lee PJ, Pusey CD, Scheinman SJ, Tam FW. Glomerular protein sieving and implications for renal failure in Fanconi syndrome. Kidney Int. Nov 2001;60(5):1885-92. [Medline].

  9. Hamm LL, Batuman V. Edema in the nephrotic syndrome: new aspect of an old enigma. J Am Soc Nephrol. Dec 2003;14(12):3288-9. [Medline].

  10. Rostoker G, Behar A, Lagrue G. Vascular hyperpermeability in nephrotic edema. Nephron. Jul 2000;85(3):194-200. [Medline].

  11. Mahmoodi BK, ten Kate MK, Waanders F, Veeger NJ, Brouwer JL, Vogt L. High absolute risks and predictors of venous and arterial thromboembolic events in patients with nephrotic syndrome: results from a large retrospective cohort study. Circulation. Jan 15 2008;117(2):224-30. [Medline].

  12. Mittal SK, Dash SC, Tiwari SC, Agarwal SK, Saxena S, Fishbane S. Bone histology in patients with nephrotic syndrome and normal renal function. Kidney Int. May 1999;55(5):1912-9. [Medline].

  13. Kumar J, Gulati S, Sharma AP, Sharma RK, Gupta RK. Histopathological spectrum of childhood nephrotic syndrome in Indian children. Pediatr Nephrol. Jul 2003;18(7):657-60. [Medline].

  14. Ozkaya N, Cakar N, Ekim M, Kara N, Akkök N, Yalçinkaya F. Primary nephrotic syndrome during childhood in Turkey. Pediatr Int. Aug 2004;46(4):436-8. [Medline].

  15. Kazi JI, Mubarak M. Pattern of glomerulonephritides in adult nephrotic patients--report from SIUT. J Pak Med Assoc. Nov 2007;57(11):574. [Medline].

  16. Barsoum R. The changing face of schistosomal glomerulopathy. Kidney Int. 2004;66:2472-2484.

  17. Doe JY, Funk M, Mengel M, et al. Nephrotic syndrome in African children: lack of evidence for 'tropical nephrotic syndrome'?. Nephrol Dial Transplant. 2006;21:672-676.

  18. Pakasa NM, Sumaili EK. The nephrotic syndrome in the Democratic Republic of Congo. N Engl J Med. Mar 9 2006;354(10):1085-6. [Medline].

  19. Sumaili EK, Krzesinski JM, Zinga CV, Cohen EP, Delanaye P, Munyanga SM, et al. Prevalence of chronic kidney disease in Kinshasa: results of a pilot study from the Democratic Republic of Congo. Nephrol Dial Transplant. Jan 2009;24(1):117-22. [Medline].

  20. Arneil GC, Lam CN. Long-term assessment of steroid therapy in childhood nephrosis. Lancet. Oct 15 1966;2(7468):819-21. [Medline].

  21. Donadio JV Jr, Torres VE, Velosa JA, Wagoner RD, Holley KE, Okamura M. Idiopathic membranous nephropathy: the natural history of untreated patients. Kidney Int. Mar 1988;33(3):708-15. [Medline].

  22. du Buf-Vereijken PW, Branten AJ, Wetzels JF. Idiopathic membranous nephropathy: outline and rationale of a treatment strategy. Am J Kidney Dis. Dec 2005;46(6):1012-29. [Medline].

  23. Jude EB, Anderson SG, Cruickshank JK, et al. Natural history and prognostic factors of diabetic nephropathy in type 2 diabetes. Quart J Med. 2002;95:371-7. [Medline].

  24. Kopp JB, Winkler C. HIV-associated nephropathy in African Americans. Kidney Int Suppl. Feb 2003;S43-9. [Medline].

  25. Bonilla-Felix M, Parra C, Dajani T, Ferris M, Swinford RD, Portman RJ. Changing patterns in the histopathology of idiopathic nephrotic syndrome in children. Kidney Int. May 1999;55(5):1885-90. [Medline].

  26. Lefaucheur C, Stengel B, Nochy D, et al. Membranous nephropathy and cancer: Epidemiologic evidence and determinants of high-risk cancer association. Kidney Int. Oct 2006;70(8):1510-7. [Medline].

  27. George BA, Zhou XJ, Toto R. Nephrotic syndrome after bevacizumab: case report and literature review. Am J Kidney Dis. Feb 2007;49(2):e23-9. [Medline].

  28. Cohen EP, Lemann J. The role of the laboratory in evaluation of kidney function. Clin Chem. 1991;37:785-796.

  29. Gupta K, Iskandar SS, Daeihagh P, et al. Distribution of pathologic findings in individuals with nephrotic proteinuria according to serum albumin. Nephrol Dial Transplant. May 2008;23(5):1595-9. [Medline].

  30. Varghese SA, Powell TB, Budisavljevic MN, et al. Urine biomarkers predict the cause of glomerular disease. J Am Soc Nephrol. 2007;18:913-22. [Medline].

  31. Rapola J. Congenital nephrotic syndrome. Pediatr Nephrol. Jul 1987;1(3):441-6. [Medline].

  32. Appel GB, Blum CB, Chien S, Kunis CL, Appel AS. The hyperlipidemia of the nephrotic syndrome. Relation to plasma albumin concentration, oncotic pressure, and viscosity. N Engl J Med. Jun 13 1985;312(24):1544-8. [Medline].

  33. Curry RC Jr, Roberts WC. Status of the coronary arteries in the nephrotic syndrome. Analysis of 20 necropsy patients aged 15 to 35 years to determine if coronary atherosclerosis is accelerated. Am J Med. Aug 1977;63(2):183-92. [Medline].

  34. Tessitore N, Bonucci E, D'Angelo A, Lund B, Corgnati A, Lund B, et al. Bone histology and calcium metabolism in patients with nephrotic syndrome and normal or reduced renal function. Nephron. 1984;37(3):153-9. [Medline].

  35. Gulati S, Godbole M, Singh U, Gulati K, Srivastava A. Are children with idiopathic nephrotic syndrome at risk for metabolic bone disease?. Am J Kidney Dis. Jun 2003;41(6):1163-9. [Medline].

  36. Leonard MB, Feldman HI, Shults J, Zemel BS, Foster BJ, Stallings VA. Long-term, high-dose glucocorticoids and bone mineral content in childhood glucocorticoid-sensitive nephrotic syndrome. N Engl J Med. Aug 26 2004;351(9):868-75. [Medline].

  37. Palmer SC, Nand K, Strippoli GF. Interventions for minimal change disease in adults with nephrotic syndrome. Cochrane Database Syst Rev. Jan 23 2008;CD001537. [Medline].

  38. Savin VJ, McCarthy ET, Sharma R, Charba D, Sharma M. Galactose binds to focal segmental glomerulosclerosis permeability factor and inhibits its activity. Transl Res. Jun 2008;151(6):288-92. [Medline].

  39. Alkjaersig N, Fletcher AP, Narayanan M, Robson AM. Course and resolution of the coagulopathy in nephrotic children. Kidney Int. Mar 1987;31(3):772-80. [Medline].

  40. Bergesio F, Ciciani AM, Santostefano M, et al. Renal involvement in systemic amyloidosis-an Italian retrospective study on epidemiological and clinical data at diagnosis. Nephrol Dial Transplant. 2007;22:1608-1618. [Medline].

  41. Brukamp K, Doyle AM, Bloom RD, Bunin N, Tomaszewski JE, Cizman B. Nephrotic syndrome after hematopoietic cell transplantation: do glomerular lesions represent renal graft-versus-host disease?. Clin J Am Soc Nephrol. Jul 2006;1(4):685-94. [Medline].

  42. Cattran DC, Alexopoulos E, Heering P, Hoyer PF, Johnston A, Meyrier A, et al. Cyclosporin in idiopathic glomerular disease associated with the nephrotic syndrome : workshop recommendations. Kidney Int. Dec 2007;72(12):1429-47. [Medline].

  43. Chesney RW, Novello AC. Forms of nephrotic syndrome more likely to progress to renal impairment. Pediatr Clin North Am. Jun 1987;34(3):609-27. [Medline].

  44. Deen WM. What determines glomerular capillary permeability?. J Clin Invest. Nov 2004;114(10):1412-4. [Medline].

  45. Eddy AA, Symons JM. Nephrotic syndrome in childhood. Lancet. Aug 23 2003;362(9384):629-39. [Medline].

  46. Filler G, Young E, Geier P. Is there really an increase in non-minimal change nephrotic syndrome in children?. Am J Kidney Dis. Dec 2003;42(6):1107-13.

  47. Fliser D, Zurbruggen, Mutschler E, et al. Coadministration of albumin and furosemide in patients with the nephrotic syndrome. Kidney Int. 1999;55:629-634. [Medline].

  48. Gorensek MJ, Lebel MH, Nelson JD. Peritonitis in children with nephrotic syndrome. Pediatrics. Jun 1988;81(6):849-56. [Medline].

  49. Grundy SM, Vega GL. Rationale and management of hyperlipidemia of the nephrotic syndrome. Am J Med. Nov 1989;87(5N):3N-11N. [Medline].

  50. Haws RM, Baum M. Efficacy of albumin and diuretic therapy in children with nephrotic syndrome. Pediatrics. Jun 1993;91(6):1142-6. [Medline].

  51. Hodson EM, Craig JC, Willis NS. Evidence-based management of steroid-sensitive nephrotic syndrome. Pediatr Nephrol. Nov 2005;20(11):1523-30. [Medline].

  52. Hoyer PF, Gonda S, Barthels M, et al. Thromboembolic complications in children with nephrotic syndrome. Risk and incidence. Acta Paediatr Scand. Sep 1986;75(5):804-10. [Medline].

  53. Ingulli E, Tejani A. Racial differences in the incidence and renal outcome of idiopathic focal segmental glomerulosclerosis in children. Pediatr Nephrol. Jul 1991;5(4):393-7. [Medline].

  54. Keane WF, St Peter JV, Kasiske BL. Is the aggressive management of hyperlipidemia in nephrotic syndrome mandatory?. Kidney Int (suppl). 1992;38:s134-s141. [Medline].

  55. Koskimies O, Vilska J, Rapola J, Hallman N. Long-term outcome of primary nephrotic syndrome. Arch Dis Child. Jul 1982;57(7):544-8. [Medline].

  56. Lewis MA, Baildom EM, Davis N, et al. Nephrotic syndrome: from toddlers to twenties. Lancet. Feb 4 1989;1(8632):255-9. [Medline].

  57. Mendoza SA, Tune BM. Management of the difficult nephrotic patient. Pediatr Clin North Am. Dec 1995;42(6):1459-68. [Medline].

  58. Mongeau JG, Corneille L, Robitaille P, et al. Primary nephrosis in childhood associated with focal glomerular sclerosis: is long-term prognosis that severe?. Kidney Int. Dec 1981;20(6):743-6. [Medline].

  59. Niaudet P, Broyer M, Habib R. Treatment of idiopathic nephrotic syndrome with cyclosporin A in children. Clin Nephrol. 1991;35 Suppl 1:S31-6. [Medline].

  60. Ozanne P, Francis RB, Meiselman HJ. Red blood cell aggregation in nephrotic syndrome. Kidney Int. Mar 1983;23(3):519-25. [Medline].

  61. Salcedo JR, Thabet MA, Latta K, Chan JC. Nephrosis in childhood. Nephron. 1995;71(4):373-85. [Medline].

  62. Southwest Pediatric Nephrology Study Group. Childhood nephrotic syndrome associated with diffuse mesangial hypercellularity. A report of the Southwest Pediatric Nephrology Study Group. Kidney Int. Jul 1983;24(1):87-94. [Medline].

  63. Swaminathan S, Leung N, Lager DJ, Melton LJ 3rd, Bergstralh EJ, Rohlinger A. Changing incidence of glomerular disease in Olmsted County, Minnesota: a 30-year renal biopsy study. Clin J Am Soc Nephrol. May 2006;1(3):483-7. [Medline].

  64. Tejani A, Nicastri AD, Sen D, et al. Long-term evaluation of children with nephrotic syndrome and focal segmental glomerular sclerosis. Nephron. 1983;35(4):225-31. [Medline].

  65. Waldman M, Crew RJ, Valeri A, Busch J, Stokes B, Markowitz G, et al. Adult minimal-change disease: clinical characteristics, treatment, and outcomes. Clin J Am Soc Nephrol. May 2007;2(3):445-53. [Medline].

  66. Warshaw BL, Hymes LC. Daily single-dose and daily reduced-dose prednisone therapy for children with the nephrotic syndrome. Pediatrics. May 1989;83(5):694-9. [Medline].

  67. Wyatt RJ, Marx MB, Kazee M, Holland NH. Current estimates of the incidence of steroid responsive idiopathic nephrosis in Kentucky children 1-9 years of age. Int J Pediatr Nephrol. Jun 1982;3(2):63-5. [Medline].

  68. Wynn SR, Stickler GB, Burke EC. Long-term prognosis for children with nephrotic syndrome. Clin Pediatr (Phila). Feb 1988;27(2):63-8. [Medline].

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Keywords

nephrotic syndrome, nephrotic, syndrome nephrotic, nephrosis, nephropathy, proteinuria, diabetic nephropathy, glomerulosclerosis, IgA nephropathy, focal segmental glomerulosclerosis, focal glomerulosclerosis, membranous nephropathy, minimal change disease, minimal-change disease, hypoalbuminemia, hypercholesterolemia, minimal change nephropathy, pediatric nephrotic syndrome, collagen vascular disease, IgA nephropathy, amyloidosis, congenital nephrotic syndrome Finnish type, focal segmental glomerulosclerosis

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Contributor Information and Disclosures

Author

Eric P Cohen, MD, Professor of Medicine, Nephrology Fellowship Program Director, Department of Medicine, Division of Nephrology, Medical College of Wisconsin; Nephrology Section Chief, Zablocki Veterans Affairs Hospital
Eric P Cohen, MD is a member of the following medical societies: American Society of Nephrology, Central Society for Clinical Research, International Society of Nephrology, and Radiation Research Society
Disclosure: Nothing to disclose.

Medical Editor

Laura L Mulloy, DO, FACP, Professor of Medicine, Chief, Section of Nephrology, Hypertension and Transplantation Medicine, Glover/Mealing Eminent Scholar Chair in Immunology, Medical College of Georgia
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Eleanor Lederer, MD, Consulting Staff, Louisville VA Hospital; Professor of Medicine; Interim Chief of Nephrology; Director of Nephrology Training Program; Director, Metabolic Stone Clinic; Director of Outpatient Clinics, Kidney Disease Program, University of Louisville School of Medicine
Eleanor Lederer, MD is a member of the following medical societies: American Association for the Advancement of Science, American Federation for Medical Research, American Society for Biochemistry and Molecular Biology, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, International Society of Nephrology, Kentucky Medical Association, National Kidney Foundation, and Phi Beta Kappa
Disclosure: Nothing to disclose.

CME Editor

Rebecca J Schmidt, DO, FACP, FASN, Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine
Rebecca J Schmidt, DO, FACP, FASN is a member of the following medical societies: American College of Osteopathic Internists, American College of Physicians, American Medical Association, American Society of Nephrology, International Society of Nephrology, National Kidney Foundation, Renal Physicians Association, and West Virginia State Medical Association
Disclosure: Abbott Grant/research funds Speaking and teaching; Genzyme Honoraria Consulting; Amgen Honoraria Speaking and teaching; Ortho Biotech Honoraria Speaking and teaching

Chief Editor

Vecihi Batuman, MD, FACP, FASN, Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Medicine Service, Southeast Louisiana Veterans Health Care System
Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, and International Society of Nephrology
Disclosure: Nothing to disclose.

 
 
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