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==Overview==
==Overview==
Nephrotic syndrome can occur primarily or due to systemic diseases. The most common cause of nephrotic syndrome in children is [[minimal change disease]]. The most common primary causes in adults are [[focal segmental glomerulosclerosis]] (FSGS), [[minimal change disease]], and [[membranous nephropathy]]. Approximately 30 percent of adults have secondary nephrotic syndrome due to [[diabetes mellitus]], [[SLE]], or [[amyloidosis]]. The most common cause of secondary nephrotic syndrome in adults is [[diabetes mellitus]].


==Causes==
==Causes==
===Primary causes===
Nephrotic syndrome can occur primarily or due to systemic diseases. The most common cause of nephrotic syndrome in children is [[minimal change disease]]. The most common primary causes in adults are [[focal segmental glomerulosclerosis]] (FSGS), [[minimal change disease]], and [[Membranous nephritis|membranous nephropathy]]. Approximately 30 percent of adults have secondary nephrotic syndrome due to [[diabetes mellitus]], [[SLE]], or [[amyloidosis]].<ref name="pmid15327378">{{cite journal |vauthors=Rivera F, López-Gómez JM, Pérez-García R |title=Clinicopathologic correlations of renal pathology in Spain |journal=Kidney Int. |volume=66 |issue=3 |pages=898–904 |date=September 2004 |pmid=15327378 |doi=10.1111/j.1523-1755.2004.00833.x |url=}}</ref><ref name="pmid9370176">{{cite journal |vauthors=Haas M, Meehan SM, Karrison TG, Spargo BH |title=Changing etiologies of unexplained adult nephrotic syndrome: a comparison of renal biopsy findings from 1976-1979 and 1995-1997 |journal=Am. J. Kidney Dis. |volume=30 |issue=5 |pages=621–31 |date=November 1997 |pmid=9370176 |doi= |url=}}</ref><ref name="pmid15327379">{{cite journal |vauthors=Simon P, Ramee MP, Boulahrouz R, Stanescu C, Charasse C, Ang KS, Leonetti F, Cam G, Laruelle E, Autuly V, Rioux N |title=Epidemiologic data of primary glomerular diseases in western France |journal=Kidney Int. |volume=66 |issue=3 |pages=905–8 |date=September 2004 |pmid=15327379 |doi=10.1111/j.1523-1755.2004.00834.x |url=}}</ref><ref name="pmid10793022">{{cite journal |vauthors=Braden GL, Mulhern JG, O'Shea MH, Nash SV, Ucci AA, Germain MJ |title=Changing incidence of glomerular diseases in adults |journal=Am. J. Kidney Dis. |volume=35 |issue=5 |pages=878–83 |date=May 2000 |pmid=10793022 |doi= |url=}}</ref><ref name="pmid16968733">{{cite journal |vauthors=Malafronte P, Mastroianni-Kirsztajn G, Betônico GN, Romão JE, Alves MA, Carvalho MF, Viera Neto OM, Cadaval RA, Bérgamo RR, Woronik V, Sens YA, Marrocos MS, Barros RT |title=Paulista Registry of glomerulonephritis: 5-year data report |journal=Nephrol. Dial. Transplant. |volume=21 |issue=11 |pages=3098–105 |date=November 2006 |pmid=16968733 |doi=10.1093/ndt/gfl237 |url=}}</ref><ref name="pmid14989627">{{cite journal |vauthors=Bahiense-Oliveira M, Saldanha LB, Mota EL, Penna DO, Barros RT, Romão-Junior JE |title=Primary glomerular diseases in Brazil (1979-1999): is the frequency of focal and segmental glomerulosclerosis increasing? |journal=Clin. Nephrol. |volume=61 |issue=2 |pages=90–7 |date=February 2004 |pmid=14989627 |doi= |url=}}</ref><ref name="pmid15327376">{{cite journal |vauthors=Gesualdo L, Di Palma AM, Morrone LF, Strippoli GF, Schena FP |title=The Italian experience of the national registry of renal biopsies |journal=Kidney Int. |volume=66 |issue=3 |pages=890–4 |date=September 2004 |pmid=15327376 |doi=10.1111/j.1523-1755.2004.00831.x |url=}}</ref>
Primary causes of nephrotic syndrome are usually described by the [[histology|histology]], i.e. [[minimal change disease]] (MCD), [[focal segmental glomerulosclerosis]] (FSGS) and [[membranous nephropathy]] (MN).


They are considered to be "[[Diagnosis of exclusion|diagnoses of exclusion]]", i.e. they are diagnosed only after secondary causes have been excluded.
===Primary Causes===
Primary renal disorders, such as primary [[glomerulonephritides]], may cause primary nephrotic syndrome. Differentiation between different types of glomerular diseases is often made by clinical suspicion and by renal [[biopsy]], which includes [[light microscopy]], [[immunofluorescence]], and ideally [[electron microscopy]].


===Secondary causes===
===Secondary Causes===
Secondary causes of nephrotic syndrome have the same histologic patterns as the primary causes, though may exhibit some differences suggesting a secondary cause.  
Secondary causes of renal disorders cause secondary nephrotic syndrome. The most common cause of secondary nephrotic syndrome in adults is [[diabetes mellitus]]. Shown below is a table of the causes of nephrotic syndrome by age group.<ref name="pmid12944064">{{cite journal| author=Eddy AA, Symons JM| title=Nephrotic syndrome in childhood. | journal=Lancet | year= 2003 | volume= 362 | issue= 9384 | pages= 629-39 | pmid=12944064 | doi=10.1016/S0140-6736(03)14184-0 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12944064 }} </ref>


They are usually described by the underlying cause.
====Common Causes of Nephrotic Syndrome by Age====
 
{|
====Secondary causes by histologic pattern====
! align="center" style="background:#4479BA; color: #FFFFFF;" + | Age (Years)
Membranous nephropathy (MN)<ref name=fogo>Fogo AB, Bruijn JA. Cohen AH, Colvin RB, Jennette JC. Fundamentals of Renal Pathology. Springer. ISBN 978-0387-31126-5.</ref>
! align="center" style="background:#4479BA; color: #FFFFFF;" + | Cause of Nephrotic Syndrome
*[[Hepatitis B]]
|-
*[[Sjogren's syndrome]]
! align="center" style="background:#DCDCDC;" + |< 15
*[[Systemic lupus erythematosus]] (SLE)
| align="left" style="background:#F5F5F5;" + |
*[[Diabetes mellitus]]
*[[Congenital]] nephrotic syndrome
*[[Sarcoidosis]]
*[[Minimal change disease]]
*[[Syphilis]]
*[[Focal segmental glomerulosclerosis]]
*[[Drugs]]
*[[Membranous nephropathy]]
*[[Malignancy]] (cancer)
|-
 
! align="center" style="background:#DCDCDC;" + | 15-40
Focal segmental glomerulosclerosis (FSGS)<ref name=fogo/>
| align="left" style="background:#F5F5F5;" + |
*[[Human immunodeficiency virus]] (HIV)
*[[Focal segmental glomerulosclerosis]]
*[[Diabetes mellitus]]
*[[Lupus nephritis]]
*[[Obesity]]
*[[Minimal change disease]]
*Kidney loss
*[[Membranous nephropathy]]
 
*[[Diabetic nephropathy]]
Minimal change disease (MCD)<ref name=fogo/>
*[[Pre-eclampsia]]
*[[Drugs]]
*Late [[post-infectious glomerulonephritis]]
*[[Malignancy]], especially [[Hodgkin's lymphoma]]
*[[IgA nephropathy]]
 
|-
===GN with Nephrotic Syndrome===
! align="center" style="background:#DCDCDC;" + | >40
| align="left" style="background:#F5F5F5;" + |
*[[Focal segmental glomerulosclerosis]]
*[[Membranous nephropathy]]
*[[Diabetic nephropathy]]
*[[Minimal change disease]]
*[[IgA nephropathy]]
*[[Primary amyloidosis]]
*[[Light chain deposition disease]]
*[[Benign nephrosclerosis]]
*Late [[post-infectious glomerulonephritis]]
|}
<sup>Adapted from Rose BD. Pathophysiology of renal diseases, ed. 2. New York, McGraw-Hill, 1987,p. 167</sup>


*[[Captopril]]
====Drug Induced====
*[[Cancer]]
* [[Agalsidase beta]]
*[[Diabetes Mellitus]]
* [[Certolizumab pegol]]
*[[Drugs]]
* [[Coagulation factor IX]]
*[[Hepatitis B]]
* [[Olsalazine]]
*[[Hodgkin's Lymphoma]]
* [[Sodium aurothiomalate]]
*[[Mixed Connective Tissue Disease]]
* [[Trimethadione]]
*[[Penicillamine]]
* [[Ziv-aflibercept ]]
*[[Streptococcal]] throat infection
*[[Systemic Lupus Erythematosus]]
*[[Thyroiditis]]


===Acute Glomerulonenephritis===
===Causes by Organ System===
*[[Berger's Disease]]
*[[Goodpasture's Syndrome]]
*[[Henoch-Schonlein Syndrome]]
*[[Streptococcal Infection]]
*Shunt infections
*Subacute [[Endocarditis]]
*[[Systemic Lupus Erythematosus]]
*[[Wegener's Granulomatosis]]


===Secondary===
{| style="width:80%; height:100px" border="1"
*[[Alport's Syndrome]]
| style="width:25%" bgcolor="LightSteelBlue" ; border="1" |'''Cardiovascular'''
| style="width:75%" bgcolor="Beige" ; border="1" |[[Endocarditis]]
|-
| bgcolor="LightSteelBlue" | '''Chemical/Poisoning'''
| bgcolor="Beige" | [[Gold]], [[Mercury (element)|mercury]]
|-
|- bgcolor="LightSteelBlue"
| '''Dental'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Dermatologic'''
| bgcolor="Beige" | [[Dermatomyositis]],
|-
|- bgcolor="LightSteelBlue"
| '''Drug Side Effect'''
| bgcolor="Beige" | [[Agalsidase beta]], [[Certolizumab pegol]], [[Coagulation factor IX]], [[Olsalazine]], [[Sodium aurothiomalate]], [[Trimethadione]], [[Ziv-aflibercept ]] , [[Interferon]], [[lithium]], [[Non-steroidal anti-inflammatory drug|NSAID]], [[Penicillamine]], [[Probenecid]], [[Sorafenib]]
|-
|- bgcolor="LightSteelBlue"
| '''Ear Nose Throat'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Endocrine'''
| bgcolor="Beige" | [[Diabetes mellitus]], [[thyroid disease]]
|-
|- bgcolor="LightSteelBlue"
| '''Environmental'''
| bgcolor="Beige" |No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Gastroenterologic'''
| bgcolor="Beige" |No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Genetic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Hematologic'''
| bgcolor="Beige" | [[Castleman's disease]], [[Sickle-cell disease|sickle cell anemia]]
|-
|- bgcolor="LightSteelBlue"
| '''Iatrogenic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Infectious Disease'''
| bgcolor="Beige" | [[HIV]], [[Infectious mononucleosis]], [[malaria]], [[Streptococcus|streptococcal]] infection, [[syphilis]], [[toxoplasmosis]], [[Hepatitis|viral hepatitis]]
|-
|- bgcolor="LightSteelBlue"
| '''Musculoskeletal/Orthopedic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Neurologic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Nutritional/Metabolic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Obstetric/Gynecologic'''
| bgcolor="Beige" |[[Pre-eclampsia|Preeclampsia]]
|-
|- bgcolor="LightSteelBlue"
| '''Oncologic'''
| bgcolor="Beige" |[[Leukemia]], [[lymphoma]], [[multiple myeloma]]
|-
|- bgcolor="LightSteelBlue"
| '''Ophthalmologic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Overdose/Toxicity'''
| bgcolor="Beige" | [[Heroin]]
|-
|- bgcolor="LightSteelBlue"
| '''Psychiatric'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Pulmonary'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Renal/Electrolyte'''
| bgcolor="Beige" | [[Amyloidosis]], [[Interstitial nephritis|chronic interstitial nephritis]], [[fabry's disease]], [[Goodpasture's syndrome]], oligomeganephronia, [[Proteinuria|orthostatic proteinuria]], [[renal vein thrombosis]]
|-
|- bgcolor="LightSteelBlue"
| '''Rheumatology/Immunology/Allergy'''
| bgcolor="Beige" | [[Bee sting]], [[Allergen|food allergens]], [[Graft vs. host disease]], [[Henoch-Schonlein purpura]], [[Kimura's disease]], [[mixed connective tissue disease]], [[polyarteritis nodosa]], [[rheumatoid arthritis]], [[sarcoidosis]], [[Sjögren's syndrome|Sjogren's syndrome]], [[systemic lupus erythematosus]], [[vasculitis]] 
|-
|- bgcolor="LightSteelBlue"
| '''Sexual'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Trauma'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Urologic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Miscellaneous'''
| bgcolor="Beige" |[[Lipoatrophy]], [[obesity]]
|-
|}
===Causes of Secondary Causes in Alphabetical Order===
<div style="-moz-column-count:3; column-count:3;">
*Adaptation to [[nephron]] reduction
*[[Amyloidosis]]
*[[Amyloidosis]]
*Congenital [[Nephrotic Syndrome]]
*[[Bee sting]]
*[[Castleman's disease]]
*[[Chronic interstitial nephritis]]
*[[Dermatomyositis]]
*[[Dermatomyositis]]
*[[Diabetes Mellitus]]
*[[Diabetes mellitus]]
*[[Drugs]]
*[[Endocarditis]]
*[[Endocarditis]]
*[[Fabry's Disease]]
*[[Fabry's disease]]
*[[Goodpasture's Syndrome]]
*[[Food allergens]]
*[[Gold]]
*[[Goodpasture's syndrome]]
*[[Graft vs. host disease]]
*[[Henoch-Schonlein purpura]]
*[[Henoch-Schonlein purpura]]
*[[Hepatitis]] A,B,C
*[[Heroin]]
*[[HIV]]
*[[HIV]]
*[[Infectious Mononeucliosis]]
*[[Infectious mononucleosis]]
*[[Interferon]]
*[[Kimura's disease]]
*[[Leukemia]]
*[[Lipoatrophy]]
*[[Lipoatrophy]]
*[[Lithium]]
*[[Lymphomas]]
*[[Lymphomas]]
*[[Malaria]]
*[[Malaria]]
*[[Multiple Myeloma]]
*[[Mercury]]
*Orthostatic [[Proteinuria]]
*[[Mixed connective tissue disease]]
*[[Polyarteritis Nodosa]]
*[[Multiple myeloma]]
*[[NSAID]]
*[[Obesity]]
*Oligomeganephronia
*[[Orthostatic proteinuria]]
*[[Penicillamine]]
*[[Polyarteritis nodosa]]
*[[Pre-eclampsia]]
*[[Probenecid]]
*[[Renal vein thrombosis]]
*[[Rheumatoid arthritis]]
*[[Rheumatoid arthritis]]
*[[Sarcoidosis]]
*[[Sarcoidosis]]
*[[Sickle Cell Anemia]]
*[[Sickle cell anemia]]
*[[Sjogren's Syndrome]]
*[[Sjogren's syndrome]]
*[[Sorafenib]]  
*[[Streptococcal Infection]]
*[[Streptococcal Infection]]
*[[Syphillis]]
*[[Syphillis]]
*[[Systemic Lupus Erythematosus]]
*[[Systemic lupus erythematosus]]
*[[Thyroid disease]]
*[[Toxoplasmosis]]
*[[Toxoplasmosis]]
*[[Vasculitis]]
*[[Vasculitis]]
 
*[[Viral hepatitis]]
===Miscellaneous===
</div>
*Chronic interstitial nephritis
*[[Graft vs. Host Disease]]
*[[Hypothyroidism]]
*[[Pre-eclampsia]]
*[[Renal vein thrombosis]]
*Severe [[Obesity]]
*[[Thyroiditis]]
 
==References==
==References==
{{Reflist|2}}
{{Reflist|2}}


{{WH}}
[[Category:Medicine]]
{{WS}}
[[Category:Nephrology]]
[[Category:Urology]]
[[Category:Up-To-Date]]
[[Category:Emergency medicine]]

Latest revision as of 22:57, 29 July 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mehrian Jafarizade, M.D [2], Yazan Daaboul, Serge Korjian

Overview

Nephrotic syndrome can occur primarily or due to systemic diseases. The most common cause of nephrotic syndrome in children is minimal change disease. The most common primary causes in adults are focal segmental glomerulosclerosis (FSGS), minimal change disease, and membranous nephropathy. Approximately 30 percent of adults have secondary nephrotic syndrome due to diabetes mellitus, SLE, or amyloidosis. The most common cause of secondary nephrotic syndrome in adults is diabetes mellitus.

Causes

Nephrotic syndrome can occur primarily or due to systemic diseases. The most common cause of nephrotic syndrome in children is minimal change disease. The most common primary causes in adults are focal segmental glomerulosclerosis (FSGS), minimal change disease, and membranous nephropathy. Approximately 30 percent of adults have secondary nephrotic syndrome due to diabetes mellitus, SLE, or amyloidosis.[1][2][3][4][5][6][7]

Primary Causes

Primary renal disorders, such as primary glomerulonephritides, may cause primary nephrotic syndrome. Differentiation between different types of glomerular diseases is often made by clinical suspicion and by renal biopsy, which includes light microscopy, immunofluorescence, and ideally electron microscopy.

Secondary Causes

Secondary causes of renal disorders cause secondary nephrotic syndrome. The most common cause of secondary nephrotic syndrome in adults is diabetes mellitus. Shown below is a table of the causes of nephrotic syndrome by age group.[8]

Common Causes of Nephrotic Syndrome by Age

Age (Years) Cause of Nephrotic Syndrome
< 15
15-40
>40

Adapted from Rose BD. Pathophysiology of renal diseases, ed. 2. New York, McGraw-Hill, 1987,p. 167

Drug Induced

Causes by Organ System

Cardiovascular Endocarditis
Chemical/Poisoning Gold, mercury
Dental No underlying causes
Dermatologic Dermatomyositis,
Drug Side Effect Agalsidase beta, Certolizumab pegol, Coagulation factor IX, Olsalazine, Sodium aurothiomalate, Trimethadione, Ziv-aflibercept , Interferon, lithium, NSAID, Penicillamine, Probenecid, Sorafenib
Ear Nose Throat No underlying causes
Endocrine Diabetes mellitus, thyroid disease
Environmental No underlying causes
Gastroenterologic No underlying causes
Genetic No underlying causes
Hematologic Castleman's disease, sickle cell anemia
Iatrogenic No underlying causes
Infectious Disease HIV, Infectious mononucleosis, malaria, streptococcal infection, syphilis, toxoplasmosis, viral hepatitis
Musculoskeletal/Orthopedic No underlying causes
Neurologic No underlying causes
Nutritional/Metabolic No underlying causes
Obstetric/Gynecologic Preeclampsia
Oncologic Leukemia, lymphoma, multiple myeloma
Ophthalmologic No underlying causes
Overdose/Toxicity Heroin
Psychiatric No underlying causes
Pulmonary No underlying causes
Renal/Electrolyte Amyloidosis, chronic interstitial nephritis, fabry's disease, Goodpasture's syndrome, oligomeganephronia, orthostatic proteinuria, renal vein thrombosis
Rheumatology/Immunology/Allergy Bee sting, food allergens, Graft vs. host disease, Henoch-Schonlein purpura, Kimura's disease, mixed connective tissue disease, polyarteritis nodosa, rheumatoid arthritis, sarcoidosis, Sjogren's syndrome, systemic lupus erythematosus, vasculitis
Sexual No underlying causes
Trauma No underlying causes
Urologic No underlying causes
Miscellaneous Lipoatrophy, obesity

Causes of Secondary Causes in Alphabetical Order

References

  1. Rivera F, López-Gómez JM, Pérez-García R (September 2004). "Clinicopathologic correlations of renal pathology in Spain". Kidney Int. 66 (3): 898–904. doi:10.1111/j.1523-1755.2004.00833.x. PMID 15327378.
  2. Haas M, Meehan SM, Karrison TG, Spargo BH (November 1997). "Changing etiologies of unexplained adult nephrotic syndrome: a comparison of renal biopsy findings from 1976-1979 and 1995-1997". Am. J. Kidney Dis. 30 (5): 621–31. PMID 9370176.
  3. Simon P, Ramee MP, Boulahrouz R, Stanescu C, Charasse C, Ang KS, Leonetti F, Cam G, Laruelle E, Autuly V, Rioux N (September 2004). "Epidemiologic data of primary glomerular diseases in western France". Kidney Int. 66 (3): 905–8. doi:10.1111/j.1523-1755.2004.00834.x. PMID 15327379.
  4. Braden GL, Mulhern JG, O'Shea MH, Nash SV, Ucci AA, Germain MJ (May 2000). "Changing incidence of glomerular diseases in adults". Am. J. Kidney Dis. 35 (5): 878–83. PMID 10793022.
  5. Malafronte P, Mastroianni-Kirsztajn G, Betônico GN, Romão JE, Alves MA, Carvalho MF, Viera Neto OM, Cadaval RA, Bérgamo RR, Woronik V, Sens YA, Marrocos MS, Barros RT (November 2006). "Paulista Registry of glomerulonephritis: 5-year data report". Nephrol. Dial. Transplant. 21 (11): 3098–105. doi:10.1093/ndt/gfl237. PMID 16968733.
  6. Bahiense-Oliveira M, Saldanha LB, Mota EL, Penna DO, Barros RT, Romão-Junior JE (February 2004). "Primary glomerular diseases in Brazil (1979-1999): is the frequency of focal and segmental glomerulosclerosis increasing?". Clin. Nephrol. 61 (2): 90–7. PMID 14989627.
  7. Gesualdo L, Di Palma AM, Morrone LF, Strippoli GF, Schena FP (September 2004). "The Italian experience of the national registry of renal biopsies". Kidney Int. 66 (3): 890–4. doi:10.1111/j.1523-1755.2004.00831.x. PMID 15327376.
  8. Eddy AA, Symons JM (2003). "Nephrotic syndrome in childhood". Lancet. 362 (9384): 629–39. doi:10.1016/S0140-6736(03)14184-0. PMID 12944064.