Ogniskowe segmentowe stwardnienie kłębuszków nerkowych

Ogniskowe segmentowe stwardnienie kłębuszków nerkowych
Etiologia i przyczyny

Ogniskowe segmentowe stwardnienie kłębuszków nerkowych (FSGS) to zespół morfologicznych zmian charakteryzujących się uszkodzeniem podocytów i segmentalnym stwardnieniem kłębuszków. Zgodnie z wytycznymi KDIGO, FSGS dzieli się na pierwotne, wtórne, genetyczne oraz o nieokreślonej etiologii. Pierwotne FSGS manifestuje się zespołem nerczycowym z białkomoczem ≥3,5 g/dobę i hipoalbuminemią ≤30 g/L, rozlanym zatarciem wypustek podocytów oraz brakiem identyfikowalnej przyczyny. W patogenezie kluczową rolę odgrywają krążące czynniki przepuszczalności, takie jak suPAR, CLC-1, Angptl4 czy przeciwciała anty-CD40, co potwierdza szybki nawrót choroby po przeszczepieniu nerki. Wtórne FSGS jest związane z różnorodnymi czynnikami, w tym hemodynamicznymi (np. nadciśnienie kłębuszkowe, otyłość, cukrzyca), lekami (np. inhibitory kalcyneuryny, dożylna heroina), infekcjami wirusowymi (HIV, HBV, HCV, CMV, EBV, SARS-CoV-2) oraz chorobami układowymi (toczeń, sarkoidoza). Diagnostyka genetyczna jest wskazana u pacjentów z opornością na steroidy, wywiadem rodzinnym lub cechami zespołów genetycznych, z identyfikacją ponad 60 genów, w tym NPHS1, NPHS2, ACTN4, TRPC6, WT1 oraz wariantów APOL1, które istotnie zwiększają ryzyko FSGS, zwłaszcza u osób pochodzenia afrykańskiego.

Etiologia ogniskowego segmentowego stwardnienia kłębuszków nerkowych (FSGS)

FSGS pierwotne (idiopatyczne)
FSGS wtórne
FSGS genetyczne
FSGS o nieokreślonej przyczynie

Czynniki ryzyka rozwoju FSGS
Mechanizmy patogenetyczne FSGS
Epidemiologia FSGS w kontekście etiologii
Złożoność etiologii FSGS

Kolejne rozdziały

Etiologia ogniskowego segmentowego stwardnienia kłębuszków nerkowych (FSGS)

Ogniskowe segmentowe stwardnienie kłębuszków nerkowych (FSGS) to nie pojedyncza choroba, ale zespół zmian morfologicznych charakteryzujący się uszkodzeniem podocytów i obecnością segmentalnego stwardnienia niektórych kłębuszków nerkowych. Etiologia FSGS jest złożona i może być spowodowana różnorodnymi czynnikami. Zgodnie z najnowszymi wytycznymi KDIGO (Kidney Disease: Improving Global Outcomes), FSGS można sklasyfikować jako pierwotne, wtórne, genetyczne lub o nieokreślonej przyczynie.¹²

FSGS pierwotne (idiopatyczne)

Pierwotne FSGS oznacza przypadki, w których choroba rozwija się bez wyraźnej przyczyny. Charakteryzuje się ono następującymi cechami:³⁴:

Zmiany FSGS widoczne w mikroskopie świetlnym w biopsji nerki
Rozlane zatarcie wypustek stopowatych podocytów widoczne w mikroskopie elektronowym
Zespół nerczycowy (białkomocz ≥3,5 g/dobę oraz hipoalbuminemia ≤30 g/L), często z towarzyszącą dyslipidemią i obrzękami
Brak identyfikowalnych przyczyn FSGS

Uważa się, że w patogenezie pierwotnego FSGS kluczową rolę odgrywają krążące czynniki przepuszczalności lub cytokiny, które powodują uszkodzenie podocytów i białkomocz, nawet w przeszczepionych nerkach.⁵⁶ Wśród proponowanych czynników znajdują się m.in. rozpuszczalny receptor urokinazowego aktywatora plazminogenu (suPAR), cytokina podobna do kardiotrofiny-1 (CLC-1), angiopoetyna-podobna 4 (Angptl4) oraz przeciwciała anty-CD40.⁷⁸ Najsilniejszym dowodem na istnienie czynnika krążącego jest doświadczenie nawrotu FSGS bezpośrednio (w ciągu godzin do kilku tygodni) po przeszczepieniu nerki.⁹

FSGS wtórne

Wtórne FSGS rozwija się w wyniku określonej przyczyny, która może być rozpoznana. Diagnozuje się je, gdy w biopsji nerki stwierdza się zmiany FSGS, z zatarciem wypustek stopowatych podocytów lub bez, u pacjenta z ustalonym procesem patofizjologicznym znanym jako przyczyna FSGS.¹⁰ Można wyróżnić kilka kategorii przyczyn:

Czynniki hemodynamiczne

Zmiany hemodynamiczne prowadzące do niedopasowania między obciążeniem kłębuszków a ich pojemnością (nadciśnienie kłębuszkowe) mogą być związane z:¹¹¹²

Zmniejszoną masą nerek:
- Pojedyncza nerka
- Przeszczep nerki
- Dysplazja nerek
- Agenezja nerki
- Oligomeganefronią
- Hipoplazja segmentowa
- Refluks pęcherzowo-moczowodowy
Czynnikami bez zmniejszonej masy nerek:
- Otyłość (zwłaszcza znaczna)
- Nefropatia w przebiegu niedokrwistości sierpowatokrwinkowej
- Wysoka podaż białka
- Nadużywanie androgenów
- Choroby układowe jak cukrzyca czy nadciśnienie tętnicze
- Wrodzona sinicza wada serca

Leki i toksyny

Wiele leków i substancji może powodować FSGS:¹³¹⁴¹⁵

Dożylna heroina (zanieczyszczenia)
Inhibitory kalcyneuryny (CNI) i inhibitory mTOR (mammalian target of rapamycin)
Pamidronat i inne bisfosfoniany
Lit
Steroidy anaboliczne
Doksorubicyna, daunomycyna
Terapia interferonem
Niesteroidowe leki przeciwzapalne (NLPZ)

Infekcje wirusowe

Wirusy są dobrze znaną przyczyną FSGS. Szczególnie wirus HIV powoduje toksyczne uszkodzenie podocytów i komórek nabłonkowych kanalików nerkowych.¹⁶ Inne wirusy związane z FSGS to:¹⁷¹⁸

Wirusowe zapalenie wątroby typu B i C
Parvowirus B19
Cytomegalowirus (CMV)
Wirus Epsteina-Barr (EBV)
SARS-CoV-2

Inne choroby i stany

Inne schorzenia, które mogą prowadzić do FSGS:¹⁹²⁰²¹

Nadciśnieniowa nefroskleroza
Sarkoidoza
Nefropatia popromiennia
Chłoniaki i inne nowotwory złośliwe
Toczeń układowy
Przebyte kłębuszkowe zapalenie nerek
Przewlekłe odmiedniczkowe zapalenie nerek

FSGS genetyczne

Badania genetyczne zaleca się u pacjentów z FSGS opornym na steroidy, z wywiadem rodzinnym FSGS, historią guza Wilmsa (nefroblastoma) lub innymi objawami sugerującymi zespół genetyczny, takimi jak zespół Alporta, choroba Fabry’ego lub zespół paznokciowo-rzepkowy.²²

Zidentyfikowano ponad 60 genów odpowiedzialnych za uszkodzenie podocytów i rozwój FSGS.²³ Wśród genów związanych z FSGS znajdują się:²⁴²⁵²⁶

NPHS1 – kodujący nefryną, białko tworzące barierę filtracyjną
NPHS2 – kodujący podocynę, białko występujące w podocytach
ACTN4 – kodujący alfa-aktynina-4
TRPC6 – receptor przejściowego potencjału kanionowego
INF2 – kodujący białko wiążące aktynę – forminę
WT1 – związany z guzem Wilmsa
ANLN – anilina
PLCE1 – fosfolipaza C epsilon 1
COQ6 – związany z biosyntezą koenzymu Q
ARHGAP24 – białko aktywujące GTPazę Rho
RCAN1 – regulowany przez kalcyneurynę 1
Kolagen typu IV alfa 3, 4 i 5

Szczególnie interesującym przypadkiem jest związek wariantów genu APOL1 z FSGS. Warianty ryzyka APOL1 G1 i G2 są znacznie częstsze u Afroamerykanów niż u osób rasy kaukaskiej, wśród których najczęstszy jest wariant APOL1 G0. Mechanizmy, poprzez które warianty alleli ryzyka mogą odgrywać rolę przyczynową i zwiększać ryzyko choroby nerek, pozostają nieznane, ale są związane nie tylko z FSGS o późnym początku, ale także z progresją niektórych innych chorób nerek.²⁷²⁸²⁹

FSGS o nieokreślonej przyczynie

W niektórych przypadkach, mimo przeprowadzenia dokładnej diagnostyki, nie udaje się określić przyczyny FSGS. Ta kategoria diagnozowana jest, gdy nie zidentyfikowano wtórnej przyczyny FSGS, nie ma identyfikowalnej przyczyny genetycznej, nie występuje zespół nerczycowy, a mikroskopia elektronowa nie ujawnia rozlanego zatarcia wypustek stopowatych podocytów.³⁰³¹

Czynniki ryzyka rozwoju FSGS

Istnieje kilka czynników, które mogą zwiększać ryzyko wystąpienia FSGS:³²³³³⁴

Pochodzenie etniczne – choroba występuje dwa razy częściej u osób czarnoskórych niż u osób rasy białej
Historia rodzinna – posiadanie członków rodziny z FSGS zwiększa ryzyko rozwoju choroby
Wiek – FSGS może wystąpić w każdym wieku, ale niektóre formy genetyczne objawiają się we wczesnym dzieciństwie
Niska masa urodzeniowa
Wcześniactwo
Otyłość – szczególnie znacznego stopnia
Infekcje wirusowe, zwłaszcza HIV
Choroby współistniejące jak cukrzyca, nadciśnienie tętnicze, anemia sierpowatokrwinkowa

Mechanizmy patogenetyczne FSGS

Niezależnie od przyczyny, w centrum patogenezy FSGS znajduje się uszkodzenie podocytów.³⁵ Podocyty, jako wysoko wyspecjalizowane komórki nabłonkowe z wypustkami stopowatymi, tworzą barierę filtracyjną kłębuszka. Ich uszkodzenie prowadzi do zatarcia wypustek stopowatych, zwiększonej przepuszczalności błony filtracyjnej, a w konsekwencji do białkomoczu i stwardnienia kłębuszków.³⁶

Uszkodzenie podocytów może nastąpić wskutek różnych mechanizmów:³⁷

Zmiany składników przepony szczelinowej lub zakłócenia jej struktury
Zaburzenia regulacji cytoszkieletu aktynowego
Zmiany błony podstawnej kłębuszka lub jej interakcji z podocytem
Zmiany ujemnego ładunku powierzchniowego podocytu

Wtórne mechanizmy adaptacyjne po utracie nefronów z jakiejkolwiek przyczyny mogą również powodować FSGS.³⁸ W takich przypadkach dochodzi do hiperfiltracji w pozostałych kłębuszkach, co prowadzi do ich przerostu i ostatecznie uszkodzenia.³⁹

W progresji FSGS do schyłkowej niewydolności nerek istotną rolę odgrywają cytokiny, czynniki wazoaktywne oraz stres mechaniczny.⁴⁰ Dodatkowo, obecność białek osocza w przesączu kanalikowym może bezpośrednio uszkadzać tkankę śródmiąższową.⁴¹

Epidemiologia FSGS w kontekście etiologii

FSGS jest jedną z najczęstszych przyczyn pierwotnej glomerulopatii prowadzącej do schyłkowej niewydolności nerek.⁴² Częstość występowania FSGS wzrasta w ciągu ostatnich trzech dekad zarówno u dzieci, jak i u dorosłych.⁴³

Oszacowana częstość występowania FSGS wynosi około 7 przypadków na 1 milion populacji, z ogólną chorobowością na poziomie 4%.⁴⁴ Szacuje się, że FSGS odpowiada za 40% przypadków zespołu nerczycowego u dorosłych i 20% przypadków zespołu nerczycowego u dzieci.⁴⁵

Rasa, pochodzenie etniczne i płeć mają znaczący wpływ na częstość występowania FSGS. Choroba jest częstsza u osób pochodzenia afrykańskiego, co może być związane z większą częstością występowania wariantów ryzyka genu APOL1 w tej populacji.⁴⁶⁴⁷

Częstość występowania FSGS o podłożu genetycznym jest wysoka u dzieci (20-30%), a u dorosłych waha się od około 22% u pacjentów z wywiadem rodzinnym chorób nerek do 10% u osób bez wywiadu rodzinnego lub w nieokreślonych kohortach.⁴⁸

Złożoność etiologii FSGS

Etiologia i patogeneza FSGS są niezwykle złożone. Obecne badania koncentrują się na roli podocytów i ich interakcji z komórkami nabłonkowymi torebki Bowmana. Zrozumienie mechanizmu uszkodzenia podocytów, jego progresji i możliwej regeneracji jest ważne nie tylko dla badań podstawowych, ale także dla codziennej praktyki diagnostycznej w patologii.⁴⁹

Należy podkreślić, że FSGS stanowi heterogenną grupę chorób. Oprócz krążących czynników, różne uszkodzenia mogą powodować ogniskowe i segmentowe stwardnienie. Te zmiany mogą rozwijać się w wyniku ciężkich chorób z kompleksami immunologicznymi, martwiczego półksiężycowego kłębuszkowego zapalenia nerek z niewielką ilością immunoglobulin, arterionefrosklerozy, przewlekłego odmiedniczkowego zapalenia nerek lub jakiegokolwiek uszkodzenia, które powoduje znaczne zmniejszenie liczby nefronów.⁵⁰

Zmiany genetyczne mogą zwiększać podatność na uszkodzenie po „drugim uderzeniu”, takim jak uszkodzenie wywołane lekami, infekcja lub nieprawidłowe zmiany adaptacyjne, które występują po jakiejkolwiek utracie miąższu nerek.⁵¹ Dlatego też dokładna diagnostyka przyczyn FSGS jest kluczowa dla wdrożenia odpowiedniego leczenia i rokowania.

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Materiały źródłowe

#1 Focal Segmental Glomerulosclerosis: Practice Essentials, Pathophysiology, Etiology
https://emedicine.medscape.com/article/245915-overview
FSGS can be classified as primary, genetic, secondary, or of undetermined cause. The 2021 KDIGO guidelines note that the terms primary FSGS and idiopathic FSGS had been used interchangeably but recommended abandoning the latter term. […] Primary FSGS is defined by the following: […] FSGS lesions on light microscopy of kidney biopsy specimen […] Diffuse foot process effacement on electron microscopy of kidney biopsy specimen […] Nephrotic syndrome (proteinuria 3.5 g/d plus hypoalbuminemia 30 g/L), often accompanied by dyslipidemia and edema; often sudden onset, amenable to therapy. […] No other identifiable causes of FSGS […] Genetic FSGS may be familial or sporadic. These cases may be a direct result of mutations in genes that code for slit diaphragm or podocyte proteins, or may be the indirect result of polymorphisms that make podocytes more vulnerable to damage. Examples of the former include NPHS1 and NHPS2 mutations that result in the absence of essential slit diaphragm components, which leads to severe congenital nephrotic syndrome. An example of the latter is polymorphisms in the APOL1 gene, which are usually found in individuals of African descent and that markedly increase risk for FSGS.
#2 Focal Segmental Glomerulosclerosis – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK532272/
FSGS can be classified as primary (idiopathic), genetic, or secondary. […] The causes of FSGS are classified as primary (idiopathic), genetic, or secondary, with causes including infections, drugs, and hemodynamic maladaptations. […] Primary FSGS has been associated with unidentified circulating permeability factors or cytokines that cause podocyte foot process effacement and proteinuria, even in transplanted kidneys. […] Genetic testing is recommended for patients with steroid-resistant FSGS, a family history of FSGS, a history of Wilms tumor (nephroblastoma), or other systemic signs suggestive of a genetic syndrome, such as Alport syndrome, Fabry disease, or nail-patella syndrome. […] Secondary FSGS can result from various factors, including drugs, inflammation, infections, toxins, and intrarenal or extrarenal hemodynamic alterations, all of which can initiate podocyte injury and lead to glomerulosclerosis.
#3 Focal Segmental Glomerulosclerosis: Practice Essentials, Pathophysiology, Etiology
https://emedicine.medscape.com/article/245915-overview
FSGS can be classified as primary, genetic, secondary, or of undetermined cause. The 2021 KDIGO guidelines note that the terms primary FSGS and idiopathic FSGS had been used interchangeably but recommended abandoning the latter term. […] Primary FSGS is defined by the following: […] FSGS lesions on light microscopy of kidney biopsy specimen […] Diffuse foot process effacement on electron microscopy of kidney biopsy specimen […] Nephrotic syndrome (proteinuria 3.5 g/d plus hypoalbuminemia 30 g/L), often accompanied by dyslipidemia and edema; often sudden onset, amenable to therapy. […] No other identifiable causes of FSGS […] Genetic FSGS may be familial or sporadic. These cases may be a direct result of mutations in genes that code for slit diaphragm or podocyte proteins, or may be the indirect result of polymorphisms that make podocytes more vulnerable to damage. Examples of the former include NPHS1 and NHPS2 mutations that result in the absence of essential slit diaphragm components, which leads to severe congenital nephrotic syndrome. An example of the latter is polymorphisms in the APOL1 gene, which are usually found in individuals of African descent and that markedly increase risk for FSGS.
#4 Focal segmental glomerulosclerosis (FSGS) – Symptoms, causes, treatment | National Kidney Foundation
https://www.kidney.org/kidney-topics/focal-segmental-glomerulosclerosis-fsgs
FSGS is not caused by a single disease. It can have many different causes. The scarring may happen because of an infection, or drug, or a disease that affects the entire body, like diabetes, HIV infection, sickle cell disease or lupus. FSGS can also be caused by another glomerular disease that you had before you got FSGS. FSGS has different types based on the cause. […] Primary FSGS: This type of FSGS means that the disease happened on its own without a known or obvious cause. […] Secondary FSGS: This type is caused by another disease or a drug. Examples include: viruses such as HIV or drugs such as anabolic steroids that some people use to speed up their muscle growth (these are different than steroids your doctor gives you for treatment).
#5 Focal Segmental Glomerulosclerosis – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK532272/
FSGS can be classified as primary (idiopathic), genetic, or secondary. […] The causes of FSGS are classified as primary (idiopathic), genetic, or secondary, with causes including infections, drugs, and hemodynamic maladaptations. […] Primary FSGS has been associated with unidentified circulating permeability factors or cytokines that cause podocyte foot process effacement and proteinuria, even in transplanted kidneys. […] Genetic testing is recommended for patients with steroid-resistant FSGS, a family history of FSGS, a history of Wilms tumor (nephroblastoma), or other systemic signs suggestive of a genetic syndrome, such as Alport syndrome, Fabry disease, or nail-patella syndrome. […] Secondary FSGS can result from various factors, including drugs, inflammation, infections, toxins, and intrarenal or extrarenal hemodynamic alterations, all of which can initiate podocyte injury and lead to glomerulosclerosis.
#6 Causes and pathogenesis of focal segmental glomerulosclerosis
https://pmc.ncbi.nlm.nih.gov/articles/PMC4772430/
Focal segmental glomerulosclerosis (FSGS) describes both a common lesion in progressive kidney disease, and a disease characterized by marked proteinuria and podocyte injury. […] Monogenetic forms of FSGS are largely due to alterations in structural genes of the podocyte, many of which result in early onset of disease. […] Genetic risk alleles in apolipoprotein L1 are especially prevalent in African Americans, and are linked not only to adult-onset FSGS but also to progression of some other kidney diseases. […] The recurrence of FSGS in some transplant recipients whose end-stage renal disease was caused by FSGS points to circulating factors in disease pathogenesis, which remain incompletely understood. […] In addition, infection, drug use, and secondary maladaptive responses after loss of nephrons from any cause may also cause FSGS.
#7 Pathology Outlines – Focal segmental glomerulosclerosis-general
https://www.pathologyoutlines.com/topic/kidneyfsgs.html
Recently proposed clinicopathological classification divided FSGS based on etiology into 3 categories: Primary FSGS, Secondary FSGS, Genetic FSGS. […] In primary FSGS, circulating permeability factors such as soluble urokinase receptor (suPAR), cardiotrophin-like cytokine 1 and angiopoietin-like 4 (Angptl4) have been proposed as the initiating factors of podocyte injury in primary FSGS. […] Recent description of autoantibodies (e.g., antinephrin) in patients with nephrotic syndrome, especially in MCD forms, suggested an autoimmune etiology for these forms, adding evidences to the link of MCD and primary FSGS. […] In secondary FSGS, different etiologies are recognized that either cause an excessive stress to the glomerular filtration barrier (maladaptive) or cause podocyte damage. […] Maladaptive forms can be due to systemic hypertension, obesity, increased lean body mass, renal vaso-occlusive disease, cyanotic congenital heart disease, sickle cell anemia, reduced number of functioning nephrons.
#8
https://link.springer.com/article/10.1007/s00441-021-03454-3
Additionally, the observation that plasma exchange and immunoadsorption reduce proteinuria in many cases of primary or recurrent FSGS, possibly due to removal of the pathological factor(s) and thus decrease of FSGS activity, strengthens the potential contribution of plasma intrinsic factors to the development of FSGS. […] Among these indications are the resolution of idiopathic nephrotic syndrome upon measles infection, the successful treatment with steroids, and other immune-modulating targets as well as increased levels of specific cytokines in FSGS patients plasma and urine. […] The hypothesis of B cell involvement in the pathogenesis of primary FSGS was proposed after successful treatment of FSGS patients with rituximab, a CD20 antibody, leading to B cell depletion. […] Nevertheless, analysis of the immune infiltrate of kidney biopsy samples from children with idiopathic nephrotic syndrome revealed a significantly higher number of glomerular CD20+B cells in FSGS patients. […] Elevated anti-CD40 antibody levels were detected in sera from recurrent FSGS patients and their capability of predicting the recurrence of FSGS before transplantation was evaluated.
#9
https://journals.lww.com/cjasn/fulltext/2017/03000/focal_segmental_glomerulosclerosis.18.aspx
The classification of a particular patient with FSGS relies on integration of findings from clinical history, laboratory testing, kidney biopsy, and in some patients, genetic testing. […] Identifying the etiology of FSGS guides selection of therapy and provides prognostic insight. […] The mechanism of podocyte injury in at least some patients with primary FSGS likely involves a circulating factor, possibly a cytokine that makes particular subjects susceptible. […] The best evidence for a circulating factor comes from the experience with recurrent FSGS immediately (on a scale of hours to several weeks) after kidney transplant. […] Current candidates for the recurrent FSGS factor, reviewed recently, include cardiotrophin-like cytokine factor 1, apoA1b (an isoform of ApoA1), anti-CD40 antibody, and serum urinetype plasminogen activator receptor (suPAR).
#10 Focal Segmental Glomerulosclerosis: Practice Essentials, Pathophysiology, Etiology
https://emedicine.medscape.com/article/245915-overview
Secondary FSGS is diagnosed when an FSGS lesion, with or without diffuse podocyte foot process effacement, is found on kidney biopsy in a patient with an established pathophysiologic process known to cause FSGS. A range of different factors, including drugs, infections, inflammations, toxins, and intrarenal hemodynamic alterations, can initiate injury to podocytes and lead to glomerulosclerosis. […] Drugs associated with FSGS include the following: […] Intravenous heroin […] Analgesics […] Pamidronate […] Lithium […] Anabolic steroids […] Doxorubicin, daunomycin […] Viruses associated with FSGS include the following: […] Hepatitis B and C […] HIV […] Parvovirus B19 […] Cytomegalovirus […] Hemodynamic factors in patients with reduced renal mass include the following:
#11 Focal Segmental Glomerulosclerosis – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK532272/
Factors related to decreased renal mass include solitary kidney, kidney allograft, renal dysplasia, renal agenesis, oligomeganephronia, segmental hypoplasia, and vesicoureteral reflux. […] Hemodynamic causes leading to a mismatch between glomerular load and capacity (glomerular hypertension) in patients without decreased renal mass include obesity (especially morbid obesity), sickle cell nephropathy, high protein intake, androgen abuse, and systemic diseases such as diabetes or hypertension. […] Drugs associated with FSGS include intravenous heroin (adulterant), calcineurin inhibitors (CNIs) and mammalian target of rapamycin (mTOR) inhibitors, pamidronate, lithium, anabolic steroids, doxorubicin, daunomycin, and interferon therapy. […] Viruses are well known to be associated with FSGS. HIV, in particular, causes podocyte and renal tubular epithelial cell toxicity. […] Other viruses known to cause FSGS include hepatitis B and C viruses, parvovirus B19, cytomegalovirus (CMV), and SARS-CoV-2. […] Other conditions causing FSGS include hypertensive nephrosclerosis, sarcoidosis, radiation nephritis, and lymphomas and other malignancies.
#12 Focal Segmental Glomerulosclerosis: Practice Essentials, Pathophysiology, Etiology
https://emedicine.medscape.com/article/245915-overview
Solitary kidney […] Kidney allograft […] Renal dysplasia […] Renal agenesis […] Oligomeganephronia […] Segmental hypoplasia […] Vesicoureteral reflux […] Sickle cell disease […] Advanced age […] Hemodynamic causes in patients without reduced renal mass include the following: […] Obesity (especially morbid obesity) […] Primary glomerular disease […] Systemic disorders (eg, diabetes, hypertension) […] Congenital cyanotic heart disease […] Lymphomas and other malignancies have been associated with FSGS. Scarring may lead to FSGS subsequent to postinfectious glomerulonephritis. Miscellaneous other conditions associated with FSGS include sarcoidosis and radiation nephritis.
#13 Focal Segmental Glomerulosclerosis – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK532272/
Factors related to decreased renal mass include solitary kidney, kidney allograft, renal dysplasia, renal agenesis, oligomeganephronia, segmental hypoplasia, and vesicoureteral reflux. […] Hemodynamic causes leading to a mismatch between glomerular load and capacity (glomerular hypertension) in patients without decreased renal mass include obesity (especially morbid obesity), sickle cell nephropathy, high protein intake, androgen abuse, and systemic diseases such as diabetes or hypertension. […] Drugs associated with FSGS include intravenous heroin (adulterant), calcineurin inhibitors (CNIs) and mammalian target of rapamycin (mTOR) inhibitors, pamidronate, lithium, anabolic steroids, doxorubicin, daunomycin, and interferon therapy. […] Viruses are well known to be associated with FSGS. HIV, in particular, causes podocyte and renal tubular epithelial cell toxicity. […] Other viruses known to cause FSGS include hepatitis B and C viruses, parvovirus B19, cytomegalovirus (CMV), and SARS-CoV-2. […] Other conditions causing FSGS include hypertensive nephrosclerosis, sarcoidosis, radiation nephritis, and lymphomas and other malignancies.
#14 Focal Segmental Glomerulosclerosis: Practice Essentials, Pathophysiology, Etiology
https://emedicine.medscape.com/article/245915-overview
Secondary FSGS is diagnosed when an FSGS lesion, with or without diffuse podocyte foot process effacement, is found on kidney biopsy in a patient with an established pathophysiologic process known to cause FSGS. A range of different factors, including drugs, infections, inflammations, toxins, and intrarenal hemodynamic alterations, can initiate injury to podocytes and lead to glomerulosclerosis. […] Drugs associated with FSGS include the following: […] Intravenous heroin […] Analgesics […] Pamidronate […] Lithium […] Anabolic steroids […] Doxorubicin, daunomycin […] Viruses associated with FSGS include the following: […] Hepatitis B and C […] HIV […] Parvovirus B19 […] Cytomegalovirus […] Hemodynamic factors in patients with reduced renal mass include the following:
#15 How does FSGS affect the kidneys? Symptoms and treatment
https://www.medicalnewstoday.com/articles/fsgs-kidney
FSGS is a disease that damages the glomeruli, which are the filtering units inside the kidneys that clean the blood. It leads to scarring, or sclerosis, in the kidneys. […] There are various potential causes of FSGS, and a single disease does not cause it. FSGS can be primary or secondary. […] Primary FSGS is when the condition occurs on its own and has no obvious cause. Genetics may play a role in some cases. Secondary FSGS usually occurs due to another disease or a drug, which can damage the glomeruli in the kidneys. […] Diseases that can cause FSGS include: HIV, diabetes, lupus, sickle cell disease, hepatitis C, a previous glomerular disease. […] Drugs that can cause FSGS include: anabolic steroids, lithium, interferon, pamidronate, mammalian target of rapamycin (mTOR) inhibitors, heroin.
#16 Focal Segmental Glomerulosclerosis – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK532272/
Factors related to decreased renal mass include solitary kidney, kidney allograft, renal dysplasia, renal agenesis, oligomeganephronia, segmental hypoplasia, and vesicoureteral reflux. […] Hemodynamic causes leading to a mismatch between glomerular load and capacity (glomerular hypertension) in patients without decreased renal mass include obesity (especially morbid obesity), sickle cell nephropathy, high protein intake, androgen abuse, and systemic diseases such as diabetes or hypertension. […] Drugs associated with FSGS include intravenous heroin (adulterant), calcineurin inhibitors (CNIs) and mammalian target of rapamycin (mTOR) inhibitors, pamidronate, lithium, anabolic steroids, doxorubicin, daunomycin, and interferon therapy. […] Viruses are well known to be associated with FSGS. HIV, in particular, causes podocyte and renal tubular epithelial cell toxicity. […] Other viruses known to cause FSGS include hepatitis B and C viruses, parvovirus B19, cytomegalovirus (CMV), and SARS-CoV-2. […] Other conditions causing FSGS include hypertensive nephrosclerosis, sarcoidosis, radiation nephritis, and lymphomas and other malignancies.
#17 Pathology Outlines – Focal segmental glomerulosclerosis-general
https://www.pathologyoutlines.com/topic/kidneyfsgs.html
Infection associated forms have been described in association with HIV (established), CMV (probably), parvovirus B19 (possibly), EBV (possibly), HCV (possibly), hemophagocytic syndrome (possibly), COVID-19 (established). […] Drug induced forms are secondary to pamidronate, direct acting antiviral therapy (ledipasvir, sofosbuvir), mTOR inhibitors, calcineurin inhibitors, anthracyclines, heroin (adulterants), lithium, interferon, anabolic steroids. […] In genetic FSGS, > 50 genes have been described as potential sites of mutation responsible for monogenic forms of FSGS. […] Genetic predisposing factor for the development of FSGS, especially in African American ethnicity, is recognized in APOL1 polymorphisms, for which the trigger of environmental factors (e.g., viral infection) most frequently leads to collapsing forms.
#18 Focal Segmental Glomerulosclerosis: Practice Essentials, Pathophysiology, Etiology
https://emedicine.medscape.com/article/245915-overview
Secondary FSGS is diagnosed when an FSGS lesion, with or without diffuse podocyte foot process effacement, is found on kidney biopsy in a patient with an established pathophysiologic process known to cause FSGS. A range of different factors, including drugs, infections, inflammations, toxins, and intrarenal hemodynamic alterations, can initiate injury to podocytes and lead to glomerulosclerosis. […] Drugs associated with FSGS include the following: […] Intravenous heroin […] Analgesics […] Pamidronate […] Lithium […] Anabolic steroids […] Doxorubicin, daunomycin […] Viruses associated with FSGS include the following: […] Hepatitis B and C […] HIV […] Parvovirus B19 […] Cytomegalovirus […] Hemodynamic factors in patients with reduced renal mass include the following:
#19 Focal Segmental Glomerulosclerosis – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK532272/
Factors related to decreased renal mass include solitary kidney, kidney allograft, renal dysplasia, renal agenesis, oligomeganephronia, segmental hypoplasia, and vesicoureteral reflux. […] Hemodynamic causes leading to a mismatch between glomerular load and capacity (glomerular hypertension) in patients without decreased renal mass include obesity (especially morbid obesity), sickle cell nephropathy, high protein intake, androgen abuse, and systemic diseases such as diabetes or hypertension. […] Drugs associated with FSGS include intravenous heroin (adulterant), calcineurin inhibitors (CNIs) and mammalian target of rapamycin (mTOR) inhibitors, pamidronate, lithium, anabolic steroids, doxorubicin, daunomycin, and interferon therapy. […] Viruses are well known to be associated with FSGS. HIV, in particular, causes podocyte and renal tubular epithelial cell toxicity. […] Other viruses known to cause FSGS include hepatitis B and C viruses, parvovirus B19, cytomegalovirus (CMV), and SARS-CoV-2. […] Other conditions causing FSGS include hypertensive nephrosclerosis, sarcoidosis, radiation nephritis, and lymphomas and other malignancies.
#20 Focal Segmental Glomerulosclerosis: Practice Essentials, Pathophysiology, Etiology
https://emedicine.medscape.com/article/245915-overview
Solitary kidney […] Kidney allograft […] Renal dysplasia […] Renal agenesis […] Oligomeganephronia […] Segmental hypoplasia […] Vesicoureteral reflux […] Sickle cell disease […] Advanced age […] Hemodynamic causes in patients without reduced renal mass include the following: […] Obesity (especially morbid obesity) […] Primary glomerular disease […] Systemic disorders (eg, diabetes, hypertension) […] Congenital cyanotic heart disease […] Lymphomas and other malignancies have been associated with FSGS. Scarring may lead to FSGS subsequent to postinfectious glomerulonephritis. Miscellaneous other conditions associated with FSGS include sarcoidosis and radiation nephritis.
#21 Focal Segmental Glomerulosclerosis – Specific Pathologies – Glomerular Diseases – Nephrology – Diseases – McMaster Textbook of Internal Medicine
https://empendium.com/mcmtextbook/chapter/B31.II.14.3.21.6.
Focal segmental glomerulosclerosis (FSGS) is a histologic pattern characterized by initial damage of the podocytes with progressive glomerulosclerosis and accompanying expansion of mesangial matrix. […] FSGS can be primary/idiopathic or secondary to a diverse group of causes. The cause of primary FSGS is unknown, although it is thought likely to be due to a circulating factor. Causes of secondary FSGS include hyperfiltration (reflux nephropathy, malignant hypertension, reduction of renal mass, obesity, and sickle cell anemia), drugs (heroin, pamidronate, lithium, calcineurin inhibitors, sirolimus), and viral infections (HIV, parvovirus B19, and less commonly cytomegalovirus or Epstein-Barr virus).
#22 Focal Segmental Glomerulosclerosis – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK532272/
FSGS can be classified as primary (idiopathic), genetic, or secondary. […] The causes of FSGS are classified as primary (idiopathic), genetic, or secondary, with causes including infections, drugs, and hemodynamic maladaptations. […] Primary FSGS has been associated with unidentified circulating permeability factors or cytokines that cause podocyte foot process effacement and proteinuria, even in transplanted kidneys. […] Genetic testing is recommended for patients with steroid-resistant FSGS, a family history of FSGS, a history of Wilms tumor (nephroblastoma), or other systemic signs suggestive of a genetic syndrome, such as Alport syndrome, Fabry disease, or nail-patella syndrome. […] Secondary FSGS can result from various factors, including drugs, inflammation, infections, toxins, and intrarenal or extrarenal hemodynamic alterations, all of which can initiate podocyte injury and lead to glomerulosclerosis.
#23 Indications for genetic testing in adults with focal segmental glomerulosclerosis | NefrologÃa
https://www.revistanefrologia.com/en-indications-for-genetic-testing-in-articulo-S2013251425000173
Focal segmental glomerulosclerosis (FSGS) is a histological pattern of injury that derives from various pathological processes that affect podocytes, resulting in loss of selectivity of the glomerular filtration membrane, proteinuria and the development of renal failure that progresses to end-stage kidney disease in a significant number of patients. […] Genetic causes of FSGS present significant clinical variability, complicating their identification. Genetic testing is crucial to identify FSGS of genetic cause. […] The prevalence of genetic FSGS is significant in children and considerable in adults, highlighting the importance of early diagnosis to avoid unnecessary treatments and facilitate genetic counselling. […] Massive sequencing techniques have revolutionized genetic diagnosis, allowing the identification of more than 60 genes responsible for podocyte damage.
#24 Focal segmental glomerulosclerosis – Wikipedia
https://en.wikipedia.org/wiki/Focal_segmental_glomerulosclerosis
Secondary FSGS can also be caused by toxins, including anabolic steroids and heroin. […] A number of genes have been implicated in FSGS. These include: NPHS1, which encodes the protein nephrin that contributes to the filtration barrier; NPHS2, which encodes the protein podocin found in podocytes; and INF2, which encodes the actin-binding protein formin. […] The pathogenesis of HIV-associated FSGS is unclear, but may be due to the presence of the G1/G2 risk alleles of the APOL1 gene.
#25 How does FSGS affect the kidneys? Symptoms and treatment
https://www.medicalnewstoday.com/articles/fsgs-kidney
FSGS is a disease that damages the glomeruli, which are the filtering units inside the kidneys that clean the blood. It leads to scarring, or sclerosis, in the kidneys. […] There are various potential causes of FSGS, and a single disease does not cause it. FSGS can be primary or secondary. […] Primary FSGS is when the condition occurs on its own and has no obvious cause. Genetics may play a role in some cases. Secondary FSGS usually occurs due to another disease or a drug, which can damage the glomeruli in the kidneys. […] Diseases that can cause FSGS include: HIV, diabetes, lupus, sickle cell disease, hepatitis C, a previous glomerular disease. […] Drugs that can cause FSGS include: anabolic steroids, lithium, interferon, pamidronate, mammalian target of rapamycin (mTOR) inhibitors, heroin.
#26 Familial Focal Segmental GlomeruloSclerosis (FSGS) | Duke Molecular Physiology Institute | Duke Molecular Physiology Institute
https://dmpi.duke.edu/studies/familial-focal-segmental-glomerulosclerosis-fsgs
Focal Segmental GlomeruloSclerosis (FSGS) is a disorder in the blood-filtering parts of the kidney called the glomeruli. […] FSGS is only one of many causes of kidney failure or end-stage renal disease (ESRD). […] Through these efforts our group have identified mutations in TRPC6, ANLN as causes of familial FSGS. […] In addition, we have shown that mutations in WT1 may also cause adult onset familial FSGS. […] In collaboration with other investigators, we also showed that mutations in PLCE1, COQ6, ARHGAP24 are causes of familial FSGS. […] More recently, our group showed that rare pathogenic variants in the gene RCAN1 could cause familial FSGS and other chronic kidney diseases. […] The disease, called familial focal segmental glomerulosclerosis, can lead to complete kidney failure and affects 20 percent of patients on dialysis.
#27 Causes and pathogenesis of focal segmental glomerulosclerosis
https://pmc.ncbi.nlm.nih.gov/articles/PMC4772430/
Focal segmental glomerulosclerosis (FSGS) describes both a common lesion in progressive kidney disease, and a disease characterized by marked proteinuria and podocyte injury. […] Monogenetic forms of FSGS are largely due to alterations in structural genes of the podocyte, many of which result in early onset of disease. […] Genetic risk alleles in apolipoprotein L1 are especially prevalent in African Americans, and are linked not only to adult-onset FSGS but also to progression of some other kidney diseases. […] The recurrence of FSGS in some transplant recipients whose end-stage renal disease was caused by FSGS points to circulating factors in disease pathogenesis, which remain incompletely understood. […] In addition, infection, drug use, and secondary maladaptive responses after loss of nephrons from any cause may also cause FSGS.
#28 Causes and pathogenesis of focal segmental glomerulosclerosis
https://pmc.ncbi.nlm.nih.gov/articles/PMC4772430/
Several circulating factors have been proposed to cause FSGS, including cardiotrophin-like cytokine-1 (CLC-1) and soluble urokinase plasminogen activator receptor (suPAR). […] Urokinase plasminogen activator surface receptor (uPAR) is a membrane protein that can bind urokinase-type plasminogen activator, vitronectin and integrins. […] The type of sclerosis is modified by the genetic background in experimental models and also likely in humans. […] The incidence of FSGS is increased in family members of patients with FSGS without monogenic inheritance patterns, and is more common in African Americans than in Caucasians. […] The APOL1 risk allele variants G1 and G2 are much more frequent in African Americans than in Caucasians, among whom the APOL1 variant G0 is most common. […] The mechanisms by which the risk allele variants might have a causal role and increase the risk of kidney disease remain unknown.
#29
https://journals.lww.com/cjasn/fulltext/2017/03000/focal_segmental_glomerulosclerosis.18.aspx
The identification of genetic variants in APOL1 in patients with FSGS has been an important discovery for FSGS and related diseases. […] APOL1-associated FSGS is a major form of FSGS in countries with individuals of sub-Saharan African descent. […] Emerging data support defining APOL1 FSGS as a separate category of FSGS.
#30 Focal Segmental Glomerulosclerosis: Histopathology Discussion – European Medical Journal
https://www.emjreviews.com/nephrology/article/focal-segmental-glomerulosclerosis-histopathology-discussion-j120121/
When a patient has FSGS lesions in presence of secondary factors that are known to cause FSGS, then it is termed as secondary FSGS. Secondary causes of FSGS include, but are not limited to, diabetic nephropathy, hypertensive nephrosclerosis, obesity, viral infections (including severe acute respiratory syndrome coronavirus 2, HIV, and Hepatitis C), drug induced (including due to nonsteroidal anti-inflammatory drugs, steroids, calcineurin inhibitors, mammalian target of rapamycin inhibitors, heroin, interferon-, and pamidronate), and reduced nephron number (as in age-related FSGS, renal dysplasia, surgical ablation, and reflux nephropathy). […] Mutations in podocyte or glomerular basement membrane proteins may result in genetic FSGS. The mutations may occur in proteins including podocin, nephrin, -actinin-4, and -integrin. Patients with genetic forms of FSGS may have a family history of kidney disease, and they are often young. […] When no secondary cause of FSGS is identified, there is no identifiable genetic cause, nephrotic syndrome is not present, and electron microscopy does not reveal diffuse foot process effacement, then this type of FSGS is termed as FSGS-UC.
#31 Focal segmental glomerulosclerosis (FSGS)
https://www.kidneyfund.org/all-about-kidneys/other-kidney-diseases/focal-segmental-glomerulosclerosis-fsgs
FSGS is a rare type of glomerular disease that causes scarring (sclerosis) in your kidneys. […] The exact causes of FSGS can vary. […] Primary FSGS: This type happens without a known or obvious cause. It is often linked to an abnormal response from the immune system or an unidentified factor in the blood that damages the kidney filters, but the exact cause of this factor is not always clear. […] Secondary FSGS: This type develops because of another condition or the use of certain medicines. For example, it can be triggered by problems with: How the kidneys are formed at birth, Some medicines, Viral infections like HIV, Parvovirus B19, or COVID-19. […] Genetic (also called familial) FSGS: This type is passed down through your family (inherited). If any of your family members have FSGS or show symptoms of it, your FSGS might be genetic. […] Undetermined FSGS: Sometimes, even after many tests, the exact cause of FSGS may remain unclear.
#32 Focal Segmental Glomerulosclerosis: Symptoms & Treatment
https://my.clevelandclinic.org/health/diseases/21149-focal-segmental-glomerulosclerosis-fsgs
Focal segmental glomerulosclerosis (FSGS) is a rare disease that causes scarring in your glomeruli, the tiny filters in your kidney. […] FSGS happens when small parts or sections of these tiny filters scar or harden (sclerosis). […] There are three types of focal segmental glomerulosclerosis: Primary FSGS: There’s no known reason or obvious cause for having FSGS. […] Secondary FSGS: This type occurs due to another disease or condition. Common causes could include infections, medications, drug use, sickle cell anemia or obesity. […] The genetic form of FSGS happens when the APOL1 gene mutates during fetal development. […] There can be several different causes for FSGS. People who have primary FSGS often don’t have an obvious cause. […] Secondary FSGS happens when there’s too much blood flow to your glomeruli. Many factors can cause this, including: Diseases like sickle cell anemia, diabetes and lupus. […] The life expectancy of people with FSGS varies depending on the severity of the disease. […] FSGS is a chronic disease that can’t be undone or reversed.
#33 Focal segmental glomerulosclerosis (FSGS)
https://www.kidneyfund.org/all-about-kidneys/other-kidney-diseases/focal-segmental-glomerulosclerosis-fsgs
FSGS is a rare type of glomerular disease that causes scarring (sclerosis) in your kidneys. […] The exact causes of FSGS can vary. […] Primary FSGS: This type happens without a known or obvious cause. It is often linked to an abnormal response from the immune system or an unidentified factor in the blood that damages the kidney filters, but the exact cause of this factor is not always clear. […] Secondary FSGS: This type develops because of another condition or the use of certain medicines. For example, it can be triggered by problems with: How the kidneys are formed at birth, Some medicines, Viral infections like HIV, Parvovirus B19, or COVID-19. […] Genetic (also called familial) FSGS: This type is passed down through your family (inherited). If any of your family members have FSGS or show symptoms of it, your FSGS might be genetic. […] Undetermined FSGS: Sometimes, even after many tests, the exact cause of FSGS may remain unclear.
#34 Focal Segmental Glomerulosclerosis (FSGS) | UNC Kidney Center
https://unckidneycenter.org/kidneyhealthlibrary/glomerular-disease/focal-segmental-glomerulosclerosis-fsgs/
FSGS stands for Focal Segmental Glomerulosclerosis. It is a relatively common form of kidney disease, especially in the US. Although there are several known risk factors, we dont yet know why most people develop FSGS. […] The short answer is that no one is sure. Doctors tend to put FSGS in two big categories, primary and secondary. Primary means that the disease happens on its own, for no obvious reasons. Secondary means that we think the FSGS was caused by, or is associated with, another medical condition. How the other condition caused the FSGS scarring has not been completely figured out for all diseases. These are some of the secondary causes/associations. […] Most people with the above conditions do not have FSGS. Having FSGS does NOT put you at risk for any of these conditions you do not already have. However, having family members with FSGS does increase your chances of developing it yourself. Also, the disease is twice as common in blacks than in whites.
#35 Pathogenesis of Focal Segmental Glomerulosclerosis
https://www.jpatholtm.org/journal/view.php?doi=10.4132/jptm.2016.09.21
Focal segmental glomerulosclerosis (FSGS) is characterized by focal and segmental obliteration of glomerular capillary tufts with increased matrix. […] Primary or idiopathic FSGS is considered to be related to podocyte injury, and the pathogenesis of podocyte injury has been actively investigated. Several circulating factors affecting podocyte permeability barrier have been proposed, but not proven to cause FSGS. FSGS may also be caused by genetic alterations. […] In primary FSGS, direct podocyte injury is postulated to result in sclerosis. […] Though morphologically similar, secondary FSGS develops due to varying injuries, conditions such as obesity, renal mass reduction, drug toxicity, viral infection, familial genetic background, hypertension-related injury, chronic pyelonephritis, or healing of pauciimmune necrotizing crescentic injury.
#36
https://link.springer.com/article/10.1007/s00467-006-0357-2
Focal segmental glomerulosclerosis (FSGS) is a major cause of idiopathic steroid-resistant nephrotic syndrome (SRNS) and end-stage kidney disease (ESKD). […] FSGS is the major cause of idiopathic steroid-resistant nephrotic syndrome (SRNS) in children and adults. […] FSGS may occur secondary to such disparate disease processes as HIV and obesity. […] Insight into the pathogenesis of FSGS developed over the past decade from studies of genetic mutations in mice, models of progressive glomerulosclerosis, and identification of gene mutations in some familial forms of nephrotic syndrome. […] Key in the pathogenesis of FSGS is podocyte damage and loss. […] Injury to podocytes occurs by four major mechanisms: alteration of the components of the slit diaphragm or interference with its structure, dysregulation of the actin cytoskeleton, alteration of the glomerular basement membrane or its interactions with the podocyte, or alteration of the negative surface charge of the podocyte.
#37
https://link.springer.com/article/10.1007/s00467-006-0357-2
Focal segmental glomerulosclerosis (FSGS) is a major cause of idiopathic steroid-resistant nephrotic syndrome (SRNS) and end-stage kidney disease (ESKD). […] FSGS is the major cause of idiopathic steroid-resistant nephrotic syndrome (SRNS) in children and adults. […] FSGS may occur secondary to such disparate disease processes as HIV and obesity. […] Insight into the pathogenesis of FSGS developed over the past decade from studies of genetic mutations in mice, models of progressive glomerulosclerosis, and identification of gene mutations in some familial forms of nephrotic syndrome. […] Key in the pathogenesis of FSGS is podocyte damage and loss. […] Injury to podocytes occurs by four major mechanisms: alteration of the components of the slit diaphragm or interference with its structure, dysregulation of the actin cytoskeleton, alteration of the glomerular basement membrane or its interactions with the podocyte, or alteration of the negative surface charge of the podocyte.
#38 Causes and pathogenesis of focal segmental glomerulosclerosis
https://pmc.ncbi.nlm.nih.gov/articles/PMC4772430/
Focal segmental glomerulosclerosis (FSGS) describes both a common lesion in progressive kidney disease, and a disease characterized by marked proteinuria and podocyte injury. […] Monogenetic forms of FSGS are largely due to alterations in structural genes of the podocyte, many of which result in early onset of disease. […] Genetic risk alleles in apolipoprotein L1 are especially prevalent in African Americans, and are linked not only to adult-onset FSGS but also to progression of some other kidney diseases. […] The recurrence of FSGS in some transplant recipients whose end-stage renal disease was caused by FSGS points to circulating factors in disease pathogenesis, which remain incompletely understood. […] In addition, infection, drug use, and secondary maladaptive responses after loss of nephrons from any cause may also cause FSGS.
#39 Focal Segmental Glomerulosclerosis (FSGS) – Creative Med Doses
https://creativemeddoses.com/topics-list/focal-segmental-glomerulosclerosis-fsgs/
Multiple factors/defects Glomerular injury Degeneration and Focal disruption of Podocytes Decreased Glomerular barrier integrity Protein and Lipid leakage Nonselective proteinuria Nephrotic range 3g/day Protein and Lipid trapped in foci of injury Deposition of Hyaline and Mesangial matrix Sclerosis of injured part of glomerulus Segmental Sclerosis Focal Segmental Glomerulosclerosis. […] Hypertension-related renal damage Loss of autoregulation of renal blood flow at the afferent arteriole. […] Transmission of elevated pressures to an unprotected glomerulus Leading to hyperfiltration and hypertrophy Increased fibrosis and sclerosis Eventual focal segmental glomerular sclerosis. […] FSGS and minimal change disease is associated with nephrotic syndrome, but the incidence of hematuria and hypertension is higher in individuals with FSGS. […] FSGS associated proteinuria is nonselective, and minimal change disease has selective proteinuria. […] The treatment of secondary FSGS is targeted toward slowing the disease progression and treating the underlying cause.
#40
https://link.springer.com/article/10.1007/s00467-006-0357-2
Genetic mutations seen in congenital forms of nephrotic syndrome and FSGS enabled researchers to identify specific gene mutations involved in podocyte damage. […] Certain clinical variants of FSGS are suggestive of different mechanisms of injury to the podocyte. […] For example, a circulating factor which leads to glomerular basement membrane injury has been proposed in the pathogenesis of some types of FSGS. […] Another example of alternative mechanisms of injury is collapsing FSGS, which occurs in the setting of viruses such as HIV. […] Factors resulting in the progression of FSGS to ESKD have also been the focus of recent research. […] Cytokines and vasoactive factors are believed to play a major role in the progression of FSGS. […] Mechanical stress is also believed to play a role in the progression of FSGS.
#41
https://link.springer.com/article/10.1007/s00467-006-0357-2
Another factor in the progression of FSGS is tubulointerstitial injury. […] The presence of plasma proteins in the tubular filtrate may directly injure the tubulointerstitium. […] The beneficial effects of blocking the renin-angiotensin system may not be limited to their antiproteinuric or antihypertensive effects. […] With the increasing incidence of FSGS in children, these pathways of podocyte injury and disease progression provide important targets for future intervention.
#42 Kidney Disease & Nephrotic Syndrome Risks | LIPOSORBERÂ®
https://liposorber.com/kidney-disease/
FSGS is a rare, scarring disease of the kidney that generally causes excess protein in the urine, nephrotic syndrome, and progressive kidney failure. […] Primary FSGS: This type of FSGS means that the disease happened on its own without a known or obvious cause. […] Secondary FSGS: This type is caused by another source, such as an infection, drug toxicity, diabetes, sickle cell disease, obesity, or even other kidney diseases. […] Genetic (familial) FSGS: This rare form of FSGS is caused by genetic mutations. […] Unknown FSGS: The underlying cause of FSGS cannot be determined despite the evaluation of clinical symptoms and extensive testing. […] FSGS is currently the most common primary glomerular disease causing kidney failure in the United States and the leading cause of kidney disease worldwide.
#43 FSGS – RKD – About the Disease & Find Resources
https://travere.com/our-science/therapeutic-areas/focal-segmental-glomerulosclerosis-fsgs/
Focal segmental glomerulosclerosis (FSGS) refers to scarring (sclerosis) of the glomeruli â blood vessels in the kidneys that filter wastes and excess fluids from the blood. The condition occurs in children and adults and is due to diverse causes. […] FSGS is divided into different types, depending on the cause: Primary â no known cause of FSGS, and with presence of nephrotic syndrome; Genetic â FSGS caused by abnormal genes that are inherited from a parent; Secondary â FSGS with a known cause such as viral infection, medications, or conditions that alter the structure of the kidney (e.g., systemic high blood pressure, obesity, sickle cell anemia, transplanted kidney, aging kidney); FSGS-UC â FSGS of undetermined cause, and without presence of nephrotic syndrome. […] The incidence of FSGS in the US has risen over the last 3 decades in children and adults. Race, ethnicity, and gender all have a significant effect on the incidence of FSGS. FSGS is more common in people of African ancestry. […] Although rare, FSGS is one of the most common glomerular causes of end-stage kidney disease.
#44 Focal Segmental Glomerulosclerosis – MD Searchlight
https://mdsearchlight.com/kidney-health/focal-segmental-glomerulosclerosis/
Focal segmental glomerulosclerosis, or FSGS, is a kidney disease that can be categorized into three types: primary, genetic, or secondary. […] In the primary type, also known as idiopathic, FSGS is linked to certain substances in the blood known as permeability factors or cytokines. […] As for the genetic type, its often a result of mutations or abnormalities in numerous genes, which then affect different parts of the cells in our kidneys filters. […] Finally, the secondary type comes about because of a range of factors like certain drugs (such as heroin, analgesics, steroids), viruses (like Hepatitis B and C, HIV), toxins, and changes within the kidneys themselves. […] Focal Segmental Glomerulosclerosis, also known as FSGS, is a kidney disease that seems to be increasing in prevalence worldwide.
#45 Kidney Disease & Nephrotic Syndrome Risks | LIPOSORBERÂ®
https://liposorber.com/kidney-disease/
FSGS is estimated to be responsible for 40% of adult nephrotic syndromes and 20% of pediatric nephrotic syndromes. […] Treatment for FSGS depends on the type and cause, your age, and whether you have other health conditions. […] In some people with secondary FSGS, treating the underlying condition may stop kidney damage from progressing. […] Treatments for FSGS may include: Angiotensin-converting enzyme (ACE) inhibitors: Drugs that treat high blood pressure. […] Immunosuppressive drugs: Drugs that manage the immune system response, such as cyclosporine and tacrolimus. […] Corticosteroids (e.g. Prednisone): Drugs that lowers levels of protein in the urine.
#46 FSGS – RKD – About the Disease & Find Resources
https://travere.com/our-science/therapeutic-areas/focal-segmental-glomerulosclerosis-fsgs/
Focal segmental glomerulosclerosis (FSGS) refers to scarring (sclerosis) of the glomeruli â blood vessels in the kidneys that filter wastes and excess fluids from the blood. The condition occurs in children and adults and is due to diverse causes. […] FSGS is divided into different types, depending on the cause: Primary â no known cause of FSGS, and with presence of nephrotic syndrome; Genetic â FSGS caused by abnormal genes that are inherited from a parent; Secondary â FSGS with a known cause such as viral infection, medications, or conditions that alter the structure of the kidney (e.g., systemic high blood pressure, obesity, sickle cell anemia, transplanted kidney, aging kidney); FSGS-UC â FSGS of undetermined cause, and without presence of nephrotic syndrome. […] The incidence of FSGS in the US has risen over the last 3 decades in children and adults. Race, ethnicity, and gender all have a significant effect on the incidence of FSGS. FSGS is more common in people of African ancestry. […] Although rare, FSGS is one of the most common glomerular causes of end-stage kidney disease.
#47 Causes and pathogenesis of focal segmental glomerulosclerosis
https://pmc.ncbi.nlm.nih.gov/articles/PMC4772430/
Several circulating factors have been proposed to cause FSGS, including cardiotrophin-like cytokine-1 (CLC-1) and soluble urokinase plasminogen activator receptor (suPAR). […] Urokinase plasminogen activator surface receptor (uPAR) is a membrane protein that can bind urokinase-type plasminogen activator, vitronectin and integrins. […] The type of sclerosis is modified by the genetic background in experimental models and also likely in humans. […] The incidence of FSGS is increased in family members of patients with FSGS without monogenic inheritance patterns, and is more common in African Americans than in Caucasians. […] The APOL1 risk allele variants G1 and G2 are much more frequent in African Americans than in Caucasians, among whom the APOL1 variant G0 is most common. […] The mechanisms by which the risk allele variants might have a causal role and increase the risk of kidney disease remain unknown.
#48 Indications for genetic testing in adults with focal segmental glomerulosclerosis | NefrologÃa
https://www.revistanefrologia.com/en-indications-for-genetic-testing-in-articulo-S2013251425000173
The etiology of FSGS of immunologic etiology, classically called primary FSGS; is not yet fully elucidated. In recent decades it has been assumed that it is caused by a circulating permeability factor, which is speculated to consist of a group of cytokines that abruptly alter podocyte function, increasing the permeability of the glomerular filtration membrane. […] The clinical presentation of FSGS with a genetic cause is extremely variable; with differences in age of presentation, degree of proteinuria, and progression of chronic kidney disease (CKD). […] The prevalence of genetically caused FSGS is high in children (20%-30%), the prevalence in adults ranges from around 22% in patients with a family history of kidney disease to 10% in those with no family history or in undefined cohorts.
#49 Pathogenesis of Focal Segmental Glomerulosclerosis
https://www.jpatholtm.org/journal/view.php?doi=10.4132/jptm.2016.09.21
Circulating permeability factors have been reckoned as the initiating factor of podocyte injury in primary FSGS and its recurrence after transplantation. […] FSGS, as a podocytopathy, may be caused by mutation in several genes, which are important in maintaining podocyte morphology and function. […] The etiology and pathogenesis of FSGS are very complex. Current research is focusing on the role of podocytes and interaction with PECs. Understanding the mechanism of podocyte injury, its progression and possible recovery is important not only for basic research but also for daily diagnostic pathology practice.
#50 Causes and pathogenesis of focal segmental glomerulosclerosis
https://pmc.ncbi.nlm.nih.gov/articles/PMC4772430/
FSGS is a heterogeneous disease. In addition to circulating factors, various injuries may cause focal and segmental sclerosis. […] The term primary FSGS is used for patients with primary podocyte injury (so-called podocytopathy), which is most often caused by a circulating factor. […] Segmental scars due to other causes are typically designated as secondary FSGS. […] These lesions can develop as a result of severe immune complex diseases, necrotizing crescentic pauci-immune glomerulonephritis, arterionephrosclerosis, chronic pyelonephritis or any injury that results in a substantial decrease in nephron number. […] Familial and sporadic forms of FSGS have both been linked to mutations in key podocyte molecules. […] Additional genetic susceptibilities might increase the severity of the resulting injury after second hits, such as drug-induced injury, infection or the mal-adaptive alterations that occur after any loss of kidney parenchyma.
#51 Causes and pathogenesis of focal segmental glomerulosclerosis
https://pmc.ncbi.nlm.nih.gov/articles/PMC4772430/
FSGS is a heterogeneous disease. In addition to circulating factors, various injuries may cause focal and segmental sclerosis. […] The term primary FSGS is used for patients with primary podocyte injury (so-called podocytopathy), which is most often caused by a circulating factor. […] Segmental scars due to other causes are typically designated as secondary FSGS. […] These lesions can develop as a result of severe immune complex diseases, necrotizing crescentic pauci-immune glomerulonephritis, arterionephrosclerosis, chronic pyelonephritis or any injury that results in a substantial decrease in nephron number. […] Familial and sporadic forms of FSGS have both been linked to mutations in key podocyte molecules. […] Additional genetic susceptibilities might increase the severity of the resulting injury after second hits, such as drug-induced injury, infection or the mal-adaptive alterations that occur after any loss of kidney parenchyma.