Focal segmental glomerulosclerosis

from Wikipedia, the free encyclopedia
Classification according to ICD-10
N04.1 Nephrotic Syndrome, Focal and Segmental Glomerular Lesions
- Focal and Segmental Sclerosis
N06.1 Isolated proteinuria with indication of morphological changes, focal and segmental glomerular lesions
- focal and segmental sclerosis
ICD-10 online (WHO version 2019)

The term focal segmental glomerulosclerosis (FSGS) covers a group of chronic diseases of the kidney , which is characterized by scarring (sclerosis) of the capillary loops of the kidney corpuscles (glomerulum) ( glomerulosclerosis ) that is visible under the light microscope . The distribution of changes in the kidney is focal , i.e. H. not all kidney corpuscles are affected. In the individual kidney corpuscles, not all lobules of the vascular tangle are affected; the infestation is segmental . In the electron microscope there are also changes in kidney corpuscles that are inconspicuous under the light microscope, a fusion of the foot processes of the cover cells (podocytes) of the capillary loops.

Focal segmental glomerulosclerosis leads to nephrotic syndrome in 75% of those affected , which is characterized by high protein losses via the urine (proteinuria) , water retention (edema) due to a reduction in blood proteins (hypoproteinemia) and disorders in the metabolism of blood lipids (hyperlipoproteinemia) . About 25% of those affected have increased protein excretion in the urine without any further symptoms. Red blood cells (erythrocytes) are often also detectable in the urine ( hematuria ). Hypertension is common.

Focal segmental glomerulosclerosis underlies around 10–20% of cases of nephrotic syndrome, and the incidence has increased in recent years.

The causes of focal segmental glomerulosclerosis are diverse. Congenital forms can be traced back to mutations of individual proteins in the cover cells (podocytes) of the kidney corpuscle. The cause of primary focal segmental glomerulosclerosis is possibly a previously unknown permeability factor in the blood. Secondary focal segmental glomerulosclerosis occurs in cases of heroin abuse , HIV , hepatitis C , IgA nephritis , lupus nephritis and all conditions that are associated with an overload of the kidney corpuscle due to increased filtration (hyperfiltration) such as excessive weight (obesity) , high blood pressure and a decrease in the number of kidney corpuscles due to other chronic kidney disease .

The diagnosis is made by a kidney puncture . Due to the fine tissue characteristics, several variants can be distinguished: Perihilar FSGS, TIP lesion, cell-rich variant and collapsing FSGS.

The prognosis of the disease depends on the variant of FSGS and the extent of protein excretion. If the proteinuria is below 3.5 g / day, the disease leads to the need for dialysis treatment in approx. 20% of those affected within 10 years , and in the case of proteinuria between 3.5 and 10 g / day, approx. 50% of those affected are within 6–8 years dependent on dialysis, with proteinuria over 10 g / day the end stage of the disease requiring dialysis is reached in almost all patients within 3–6 years.

Depending on the prognosis and the histological variant of FSGS, treatment is carried out with ACE inhibitors , AT1 antagonists , statins , corticosteroids , ciclosporin and, if necessary, mycophenolate mofetil .

After kidney transplantation , about 30% of patients experience a recurrence (relapse) of the disease in the transferred kidney (transplant).

Epidemiology

Focal segmental glomerulosclerosis (FSGS) is an important cause of nephrotic syndrome in adults and adolescents. In the United States, the incidence of FSGS has increased tenfold over the past twenty years and is responsible for 35% of all cases of nephrotic syndrome; in Black Americans, the proportion is 50%. FSGS is thus the most common primary glomerular disease that leads to kidney failure requiring dialysis. In other countries, FSGS is rarer and in Spain, for example, with a share of 12% of all glomerular diseases, it ranks fourth behind membranous glomerulonephritis (24%), minimal change glomerulonephritis (16%) and lupus nephritis (14%)

Classification

The FSGS is classified according to the cause or according to the tissue (histological) findings (detailed images under).

Classification by cause

Histological classification

Classic FSGS (FSGS NOS, Not Otherwise Specified)

  • Most common form
  • Changes in some, not all glomeruli (focal) detectable with light microscopy .
  • In the changed glomeruli, only some, not all segments of the vascular clusters (capillary convolute) are affected (segmental).
  • In the affected segments there is a breakdown (collapse), scarring (sclerosis) and cell proliferation of the tissue between the capillary loops ( mesangium ).
  • Due to increased permeability, plasma proteins are deposited in the form of hyaline precipitates in the capillary wall.
  • In immunofluorescence microscopy no specific deposits are demonstrated.
  • In electron microscopy , analogous to minimal change glomerulonephritis, a fusion of the foot processes of the glomerular cover cells (podocytes) can also be detected in the glomeruli, which are inconspicuous under the light microscope .
  • Since not all glomeruli show sclerotic changes, especially in the early stages, the disease can incorrectly be classified as minimal change glomerulonephritis if no glomeruli with typical changes were detected in the kidney biopsy .
  • To diagnose classic FSGS, the other histological variants must be excluded.

Collapsing variant

  • The entire capillary convolute (capillary tangle) of the glomerulus, and not just individual segments, has collapsed (shrunk) and sclerosed (scarred).
  • The cause is either unknown ( idiopathic ) or caused by an HIV infection .
  • Mostly severe, therapy-resistant nephrotic syndrome .
  • Usually rapid deterioration in kidney function .
  • Common in people of black African descent.
  • Overall bad prognosis.

Tip lesion (tip variant)

Perihilar variant (perihilar variant)

  • Changes at the vascular pole (the hilus ) of the glomerulus with scarring ( sclerosis ) and deposition of transparent material ( hyaline ) in more than 50% segmentally sclerosed glomeruli.
  • Immunohistological and electron microscopic findings as in classic FSGS.
  • Often in diseases that are associated with an overload of the glomerulus ( hyperfiltration ).

Cell rich variant (cellular variant)

  • Detection of at least one glomerulus with a segment in which capillaries are closed by cell proliferation.
  • Changes in the other glomeruli as in classic FSGS.
  • In electron microscopy, diffuse fusion of the foot processes of the podocytes .

C1q nephropathy

Main article: C1q nephropathy

Primary FSGS

Primary FSGS is similar to minimal change glomerulonephritis , but has a more severe course. Minimal change glomerulonephritis can develop into primary FSGS as the disease progresses.

Pathogenesis of primary FSGS

So far it has been assumed that primary damage to the podocytes plays a central role in the development of primary FSGS. The cause of this damage is not known. It may be a circulating toxin ; Candidates who are currently being investigated intensively, are a cytokine called cardiotrophin-like cytokine-1 (CLC-1) and soluble urokinase - receptor .

Recent studies suggest that the parietal epithelial cells of the kidney corpuscle are damaged first. This leads to activation of the epithelial cells, and there is an attachment ( adhesion ) of the capillary loops of the renal corpuscle to the activated epithelial cells. The epithelial cells migrate into the adhering segment of the loop convolute, the extracellular matrix is deposited , the podocytes perish and the segment finally becomes scarred.

Focal segmental glomerulosclerosis can possibly be differentiated from minimal change glomerulonephritis by the expression of certain proteins : the protein dystroglycan , via which the podocyte is connected to the glomerular basement membrane , is preserved in FSGS, but in minimal change GN reduced. An increased expression of fibroblast-specific protein-1 (FSP-1), on the other hand, indicates the collapsing variant of FSGS with a particularly aggressive course.

In some populations, e.g. B. in Americans of black African descent, a polymorphism in the MYH9 gene , which codes for the heavy chain of myosin , can contribute to the disease. MYH9 itself is probably not responsible for the increased risk, but rather the directly neighboring gene APOL1 . Variants of this gene give the carriers a resistance to infections with Trypanosoma brucei rhodesiense and thus a selection advantage . The APOL1 gene codes for the protein apolipoprotein LI (APOL1), which was only found in humans and gorillas. When trypanosomes ingest APOL1 through endocytosis , APOL1 forms pores in the membrane of the lysosomes , which lead to lysis of the parasite cells. The pathomechanism by which APOL1 leads to kidney damage in humans is not yet known.

In 2011, an international research group identified a receptor for the enzyme urokinase circulating in the blood as a possible cause of the disease. In a mouse model, the disease could be triggered by the receptor. When the receptor was removed from the blood by plasmapheresis , the disease progression often came to a standstill.

Clinic of primary FSGS

Typical manifestations are the acute onset of a nephrotic syndrome with water retention (edema) , albumin deficiency (hypoalbuminemia) and large protein losses via the urine (nephrotic proteinuria) . Occasionally, only non-nephrotic proteinuria is detectable with no further clinical signs. High blood pressure and detection of red blood cells (erythrocytes) in the urine ( microhematuria ) are common. The renal function may be limited. The relative frequencies are:

  • Nephrotic proteinuria: 60-75%
  • Microhematuria: 30–50%
  • High blood pressure: 45-65%
  • Renal impairment: 25–50%.

Secondary FSGS

Secondary FSGS summarizes the forms of focal sclerosis that are based on an increase in size (hypertrophy) or overload (hyperfiltration) of the kidney corpuscles as a result of previous kidney damage, which either led to a decrease in the total number of glomeruli or to an expansion of the Renal vessels ( vasodilation ) with a constant number of glomeruli. The differentiation from primary FSGS is important because the therapy is different.

Podocyte damage

As with primary FSGS, damage to the podocytes is the beginning of the changes in the glomerulus in secondary FSGS. The podocytes are damaged by circulating cytokines (e.g. TGF-β ), angiotensin II , by monocytes , inflammatory mediators or by increased pressure within the glomerulus. Because the podocytes cannot divide, dead cells are not replaced. The basement membrane is exposed, the filtration barrier, which is formed by the slit membrane of the podocytes, collapses. Large amounts of fluid and albumin are filtered, larger macromolecules such as IgM , fibrinogen and complement components , which cannot pass through the basement membrane, are deposited as hyaline depots between the endothelium and the basement membrane (subendothelial depots).

Nephron loss

Many kidney diseases can lead to the loss of nephrons , including diseases that do not primarily affect the glomeruli such as reflux nephropathy , decreased blood flow ( ischemia ) due to vascular nephropathy , loss of kidney tissue due to surgery, or congenital malformations. The loss of nephrons leads to a compensatory increase in size, increased filtration and finally scarring (sclerosis) of the remaining nephrons. The growth factor TGF-β is likely involved in the increase in the extracellular matrix .

The occurrence of secondary FSGS depends on the extent of nephron loss. If a kidney is removed due to an accident, cancer or a kidney donation, there is no loss of kidney function even after decades. World War II veterans found only a slight increase in blood pressure and proteinuria 45 years after a kidney had to be removed due to an injury. In kidney donors, no deterioration in kidney function and no increased incidence of high blood pressure or proteinuria could be detected up to 24 years after kidney donation . If more than 75% of the kidney tissue is lost or a kidney is missing from birth due to a congenital malformation, proteinuria, glomerulosclerosis and progressive deterioration in kidney function can occur.

Expansion of kidney vessels (renal vasodilation)

Diabetic nephropathy , sickle cell anemia , obesity , familial autonomic insufficiency , glycogen storage disease and preeclampsia can lead to dilation of the renal vessels, increase in pressure in the glomerulus and thus to secondary FSGS.

Healing phase after glomerulonephritis

FSGS can occur during the healing phase of inflammatory kidney diseases such as lupus nephritis , IgA nephritis, and rapid progressive glomerulonephritis . The cause may be the increased release of TGF-β .

Heroin nephropathy

When heroin -dependent, especially when black African descent, it can lead to FSGS, even if HIV infection was ruled out in those affected. Heroin nephropathy can develop into chronic kidney failure over the course of years and is therefore slower than HIV-associated FSGS, which can lead to kidney failure within months. The disease may be due to contamination of the heroin.

Other secondary forms of FSGS

FSGS has also been described in the case of improper use of anabolic steroids , treatment with lithium, and cancer , especially lymphoma .

Familial or Hereditary FSGS

Hereditary forms of FSGS may underlie a significant proportion of diseases that do not respond to steroids (steroid-resistant FSGS), especially if they occur in children. There were autosomal - dominant modes of inheritance with different penetrance described, but also autosomal recessive modes of inheritance.

Suspicious gene loci were found on

The genes identified so far code for proteins that are involved in the formation of the glomerular basement membrane and / or the differentiation and function of podocytes: Podocin, nephrin, alpha-actinin-4, TRPC6, CD2AP, inverted formin. Some mutations of these genes lead to intracellular deposits of the modified proteins.

Nephrin

Nephrin is an essential component of the slit membrane between the foot processes of the podocytes. The NPHS1 gene is on chromosome 19. Mutations in this gene lead to the congenital nephrotic syndrome of the Finnish type. A commercial test for the detection of NPHS1 mutations is available.

Podocin

Podocin is a membrane protein that is exclusively in glomerular podocytes expressed will. Podocin is involved in the expression and spatial arrangement of nephrin, the main component of the slit membrane. The NPHS2 gene is located on chromosome 1 gene locus q25-31. Mutations lead to familial FSGS with an autosomal recessive inheritance. The disease usually occurs before the age of 6. In children, steroid-resistant FSGS mutations in the NPHS2 gene were found in 10–25% of cases . Mild courses with first onset in adolescence or young adulthood have been described. Unexpectedly, a recurrence in the transplant has been described after kidney transplantation. A commercial test for the detection of NPHS2 mutations is available.

TRPC6

TRPC6 is a calcium - permeable cation channel , which is expressed in podocytes on the slit membrane and which is necessary for an adequate structure and function of the podocytes. The gene for TRPC6 is on chromosome 11 . Mutations lead to familial FSGS with an autosomal dominant inheritance.

Alpha-actinin-4

Alpha-actinin-4 is involved in building the cytoskeleton . The gene for alpha-actinin-4 is located on chromosome 19 gene locus q13. Mutations lead to familial FSGS with an autosomal dominant inheritance. Mutated alpha-actinin-4 binds to actin more strongly than the wild type and thus possibly leads to changes in the cytoskeleton of the podocytes.

CD2AP

CD2AP is a protein that interacts with podocin and nephrin in the slit membrane. Mutations in the gene for CD2AP have so far been described in two patients with primary FSGS.

Inverted formin

Inverted formin is a protein that plays an important role in the formation of actin filaments. Mutations in the gene for inverted formin were found in eleven unrelated families with autosomal dominant focal segmental glomerulosclerosis.

Myosin-Ie

Myosin-Ie is a Class I myosin that is expressed in the podocyte membrane of the kidney corpuscle . Myosin-Ie is encoded by the MYO1E gene. Mutations in this gene lead to focal segmental glomerulosclerosis, which manifests itself in childhood.

Differential diagnosis of FSGS

It is important to distinguish between the different forms of FSGS:

  • Primary FSGS may respond well to immunosuppressive therapy .
  • Secondary FSGS, on the other hand, is treated with drugs that lower the pressure in the glomerulus.

There are indications of the cause of the FSGS

  • from the medical history ( anamnesis ), if z. B. there are other diseases that may be the basis of FSGS
  • from the time course of the onset of the disease
  • from the level of proteinuria
  • from the electron microscopic findings.

Acute onset of a nephrotic syndrome with water retention (edema) and a reduction in the albumin level in the blood (hypalbuminemia) are more indicative of primary FSGS. Secondary FSGS, on the other hand, is usually characterized by slowly rising, non-nephrotic proteinuria in connection with progressive deterioration in kidney function ; Edema and hypoalbuminaemia are rather uncommon in secondary.

In the case of primary FSGS, electron microscopic examination reveals diffusely changed podocytes with fusion of the foot processes in glomeruli, which are inconspicuous under the light microscope . In secondary FSGS, a fusion of the foot processes is usually only found in the glomeruli, which also appear changed under the light microscope.

The delimitation of the familial forms is particularly difficult. Indications of hereditary FSGS are a lack of response to therapy with corticosteroids , nephrotic syndrome or proteinuria in other family members ( positive family history ) and the onset of the disease in infancy or early childhood.

Therapy and prognosis of FSGS

Primary FSGS

If left untreated, FSGS leads to loss of kidney function in patients with nephrotic syndrome, requiring dialysis treatment . Immunosuppressive treatment leads to a partial or complete decrease in proteinuria ( partial or complete remission ) in around 70% of those affected . The success of the therapy does not depend on the histological variant of the disease.

The first choice drug is prednisone . The duration of therapy depends on the response to treatment, but is generally longer than treatment for minimal change nephropathy .

Cyclosporine is given to patients who do not tolerate prednisone .

Patients with non-nephrotic proteinuria (<3.5 mg / d) are usually not treated immunosuppressively.

A first relapse after complete remission can be treated again with prednisone.

If relapses occur frequently, low-dose prednisone in combination with cyclosporine can be used.

Patients who do not respond to prednisone are treated with cyclosporine, possibly in combination with prednisone.

Patients who do not respond to prednisone or cyclosporine, or who do not tolerate this treatment, can be treated with mycophenolate mofetil .

Treatment with ACE inhibitors and / or AT1 antagonists is recommended for all patients with FSGS, especially if immunosuppressive treatment is not possible or (in non-nephrotic proteinuria) not necessary.

If the nephrotic syndrome or renal impairment persists, treatment with a statin to lower high cholesterol levels is recommended.

Treatment with cyclophosphamide , tacrolimus , sirolimus, and plasmapheresis is usually not recommended as there is limited experience with these therapies.

An experimental study with five patients with primary or relapsed FSGS who had B7-1-positive podocytes showed a partial or complete remission of proteinuria in all patients under treatment with abatacept , a fusion protein of the peptide CTLA and immunoglobulin . Abatacept is an inhibitor of the costimulatory B7-1 molecule on the T cell , which is already used successfully in the treatment of rheumatoid arthritis .

Secondary FSGS

Immunosuppressive treatment is not advisable in secondary FSGS. In addition to treating the underlying disease (e.g. HIV infection), ACE inhibitors, AT1 antagonists and statins are given.

further reading

  • Role of podocytes in focal sclerosis: defining the point of no return . In: J Am Soc Nephrol , 2005, 16 (10), pp. 2830-2832, PMID 16148037
  • Stephen M Korbet: Treatment of primary focal segmental glomerulosclerosis . In: Kidney International . 62, No. 6, December 2002, ISSN  0085-2538 , pp. 2301-2310. doi : 10.1046 / j.1523-1755.2002.00674.x . PMID 12427162 .
  • Slit or pore? A mutation of the ion channel TRPC6 causes FSGS . In: Nephrol Dial Transplant , 20 (9), 2005, pp. 1777-1779, PMID 15998650
  • Nephrotic focal segmental glomerulosclerosis in 2004: an update . In: Nephrol Dial Transplant , 19 (10), 2004, pp. 2437-2444, PMID 15280528
  • Focal segmental glomerulosclerosis in adults . In: Nephrol Dial Transplant , 18 Suppl 6, 2003, pp. Vi45-51, PMID 12953042
  • Pathology of minimal change nephropathy and segmental sclerosing glomerular disorders . In: Nephrol Dial Transplant , 18 Suppl 6, 2003, pp. Vi33-38, PMID 12953040
  • Treatment of primary focal segmental glomerulosclerosis . In: Nephrol Dial Transplant , 14 Suppl 3, 1999, pp. 74-78, PMID 10382986
  • Clinical picture and outcome of primary focal segmental glomerulosclerosis . In: Nephrol Dial Transplant , 14 Suppl 3, 1999, pp. 68-73, PMID 10382985
  • Secondary focal and segmental glomerulosclerosis . In: Nephrol Dial Transplant , 14 Suppl 3, 1999, pp. 58-67, PMID 10382984
  • Morphological features of primary focal and segmental glomerulosclerosis . In: Nephrol Dial Transplant , 14 Suppl 3, 1999, pp. 53-57, PMID 10382983
  • The many masks of focal segmental glomerulosclerosis . Kidney Int 46 (4), 1994, pp. 1223-1241, PMID 7861720
  • Editorial: Focal glomerular sclerosis . Kidney Int 4 (6), 1973, pp. 355-361, PMID 4130965
  • Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group . KDIGO Clinical Practice Guideline for Glomerulonephritis. In: Kidney inter Suppl . No. 2 , 2012, p. 139–274 (English, clinical guidelines ).

Web links

Individual evidence

  1. Vivette D D'Agati et al .: Pathologic classification of focal segmental glomerulosclerosis: a working proposal . In: Am J Kidney Dis . No. 43 , 2004, p. 368-382 ( Article ).
  2. Christina M Wyatt, Paul E Klotman, Vivette D D'Agati: HIV-associated nephropathy: clinical presentation, pathology, and epidemiology in the era of antiretroviral therapy . In: Seminars in Nephrology . 28, No. 6, November 2008, ISSN  0270-9295 , pp. 513-522. doi : 10.1016 / j.semnephrol.2008.08.005 . PMID 19013322 .
  3. Ellen T McCarthy, et al .: Circulating permeability factors in idiopathic nephrotic syndrome and focal segmental glomerulosclerosis . In: Clinical Journal of the American Society of Nephrology . 5, No. 11, November 2010, ISSN  1555-905X , pp. 2115-2121. doi : 10.2215 / CJN.03800609 . PMID 20966123 .
  4. Bart Smeets, et al .: Parietal epithelial cells participate in the formation of sclerotic lesions in focal segmental glomerulosclerosis . In: Journal of the American Society of Nephrology . 22, No. 7, July 2011, ISSN  1533-3450 , pp. 1262-1274. doi : 10.1681 / ASN.2010090970 . PMID 21719782 .
  5. Giovanna Giannico, Haichun Yang, Eric G Neilson, Agnes B Fogo: dystroglycan in the diagnosis of FSGS . In: Clinical Journal of the American Society of Nephrology: CJASN . 4, No. 11, November 2009, ISSN  1555-905X , pp. 1747-1753. doi : 10.2215 / CJN.01510209 . PMID 19808230 .
  6. Jeffrey B Kopp, et al .: MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis . In: Nature Genetics . 40, No. 10, October 2008, ISSN  1546-1718 , pp. 1175-1184. doi : 10.1038 / ng.226 . PMID 18794856 .
  7. ^ Giulio Genovese, et al .: Association of trypanolytic ApoL1 variants with kidney disease in African Americans . In: Science . 329, No. 5993, August 13, 2010, ISSN  1095-9203 , pp. 841-845. doi : 10.1126 / science.1193032 . PMID 20647424 .
  8. Pays E, Vanhollebeke B, Vanhamme L, Paturiaux-Hanocq F, Nolan DP, Pérez-Morga D. The trypanolytic factor of human serum. In: Nat Rev Microbiol . , 2006 Jun, 4 (6), pp. 477-486, PMID 16710327
  9. Changli Wei, Shafic El Hindi, Jing Li, Alessia Fornoni, Nelson Goes: Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis . In: Nat Med . 2011 Jul 31, doi: 10.1038 / nm.2411 , PMID 21804539
  10. Primary focal segmental glomerulosclerosis . In: J Am Soc Nephrol 9 (7), 1998, pp. 1333-1340, PMID 9644647
  11. Leal C. Herlitz, et al .: Development of focal segmental glomerulosclerosis after anabolic steroid abuse . In: Journal of the American Society of Nephrology: JASN . 21, No. 1, January 2010, ISSN  1533-3450 , pp. 163-172. doi : 10.1681 / ASN.2009040450 . PMID 19917783 .
  12. Inherited podocytopathies: FSGS and nephrotic syndrome from a genetic viewpoint . In: J Am Soc Nephrol , 13 (12), 2002, pp. 3016-3023, PMID 12444222
  13. Nephrin.  In: Online Mendelian Inheritance in Man . (English).
  14. Podocin.  In: Online Mendelian Inheritance in Man . (English).
  15. TRPC6.  In: Online Mendelian Inheritance in Man . (English).
  16. Alpha-actinin-4.  In: Online Mendelian Inheritance in Man . (English).
  17. CD2AP.  In: Online Mendelian Inheritance in Man . (English).
  18. INF2.  In: Online Mendelian Inheritance in Man . (English).
  19. Elizabeth J Brown, Johannes S Schlöndorff, Daniel J Becker, Hiroyasu Tsukaguchi, Andrea L Uscinski, Henry N Higgs, Joel M Henderson, Martin R Pollak, Stephen J Tonna: Mutations in the formin gene INF2 cause focal segmental glomerulosclerosis . In: Nature Genetics . 42, No. 1, January 2010, ISSN  1546-1718 , pp. 72-76. doi : 10.1038 / ng.505 . PMID 20023659 .
  20. MYOSIN IE.  In: Online Mendelian Inheritance in Man . (English)
  21. Caterina Mele, et al .: MYO1E mutations and childhood familial focal segmental glomerulosclerosis . In: The New England Journal of Medicine . 365, No. 4, July 28, 2011, ISSN  1533-4406 , pp. 295-306. doi : 10.1056 / NEJMoa1101273 . PMID 21756023 .
  22. Micky J Chun, Stephen M Korbet, Melvin M Schwartz, Edmund J Lewis: Focal segmental glomerulosclerosis in nephrotic adults: presentation, prognosis, and response to therapy of the histologic variants . In: Journal of the American Society of Nephrology: JASN . 15, No. 8, August 2004, ISSN  1046-6673 , pp. 2169-2177. doi : 10.1097 / 01.ASN.0000135051.62500.97 . PMID 15284302 .
  23. Primary focal segmental glomerulosclerosis: clinical course, predictors of renal outcome and treatment . In: Intern Med , 39 (8), 2000, pp. 606-611, PMID 10939532
  24. ^ Update on the treatment of idiopathic FSGS. Alain Meyrier, Paris, France. Chair: Peter Mathieson, Bristol, UK, Caroline Savage, Birmingham, UK ( Memento of the original from July 7, 2010 in the Internet Archive ) Info: The archive link has been inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. , NDT Educational; CME Slides Forum 2nd December 2010 Update ( Memento of the original from July 7th 2010 in the Internet Archive ) Info: The archive link was automatically inserted and not yet checked. Please check the original and archive link according to the instructions and then remove this notice. Presentation  ( page no longer available , search in web archivesInfo: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice. engl. @1@ 2Template: Webachiv / IABot / www.ndt-educational.org @1@ 2Template: Webachiv / IABot / www.ndt-educational.org @1@ 2Template: Toter Link / www.ndt-educational.org  
  25. Chih-Chuan Yu, Alessia Fornoni, Astrid Weins, Samy Hakroush, Dony Maiguel, Junichiro Sageshima, Linda Chen, Gaetano Ciancio, Mohd. Hafeez Faridi, Daniel Behr, Kirk N. Campbell, Jer-Ming Chang, Hung-Chun Chen, Jun Oh, Christian Faul, M. Amin Arnaout, Paolo Fiorina, Vineet Gupta, Anna Greka, George W. Burke, III, Peter Mundel : Abatacept in B7-1-Positive Proteinuric Kidney Disease New England Journal of Medicine 2013, Volume 369, Issue 25, December 19, 2013, pages 2416-2423; doi: 10.1056 / NEJMoa1304572