A Review of Focal Segmental Glomerulosclerosis Classification With a Focus on Genetic Associations

Kidney Medicine, Год журнала: 2024, Номер 6(6), С. 100826 - 100826

Опубликована: Апрель 17, 2024

Focal segmental glomerulosclerosis (FSGS) defines a distinct histological pattern observed in kidney tissue, that is linked to several underlying causes, all converging on the common factor of podocyte injury. It presents considerable challenge terms classification due its varied causes and limited correlation between histopathology clinical outcomes. Critically, precise nomenclature key describe delineate pathogenesis, subsequently guiding selection suitable precision therapies. A proposed pathomechanism-based approach has been suggested for FSGS classification. This differentiates primary, secondary, genetic, undetermined aiming provide clarity. Genetic from monogenic mutations can emerge during childhood or adulthood, it advisable conduct genetic testing cases where there family history chronic disease, nephrotic syndrome, resistance treatment. Genome-wide association studies have identified risk variants, such as apolipoprotein L1 (APOL1), which play role development FSGS. Currently, no specific treatments approved treat FSGS; however, interventions targeting cofactor deficiencies shown potential some cases. Furthermore, encouraging results emerged phase 2 trial investigating inaxaplin, novel small molecule APOL1 channel inhibitor, APOL1-associated

Язык: Английский

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Therapeutic Potential Targeting Podocyte Mitochondrial Dysfunction in Focal Segmental Glomerulosclerosis

Kidney Diseases, Год журнала: 2023, Номер 9(4), С. 254 - 264

Опубликована: Янв. 1, 2023

Podocytes are essential components of the glomerular filtration barrier and for proper function glomerulus. Podocyte injury under various stress conditions is primary pathogenesis key determinant focal segmental glomerulosclerosis (FSGS) with prominent clinical manifestations proteinuria or nephrotic syndrome.Under physiological conditions, a highly coordinated mitochondrial quality control system, including antioxidant defenses, dynamics (fusion, fission, mitophagy), biogenesis, guarantees sophisticated structure functions podocytes. However, FSGS pathological mitochondria encounter oxidative stress, disturbances, defective biogenesis. Moreover, mutations in DNA mitochondria-related genes also strongly associated FSGS. Based on these pieces evidence, bioactive agents that to relieve promote biogenesis have been proven effective preclinical models. Targeting network expected provide new therapeutic strategies treatment delay its progression end-stage renal disease.Mitochondrial dysfunction plays role podocyte progression. This review summarized recent advances study homeostatic imbalance discussed potential mitochondria-targeted therapeutics improving retarding disease.

Язык: Английский

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Pathogenesis of Focal Segmental Glomerulosclerosis and Related Disorders

Annual Review of Pathology Mechanisms of Disease, Год журнала: 2025, Номер 20(1), С. 329 - 353

Опубликована: Янв. 24, 2025

Focal segmental glomerulosclerosis (FSGS) is the morphologic manifestation of a spectrum kidney diseases that primarily impact podocytes, cells create filtration barrier glomerulus. As its name implies, only parts and glomeruli are affected, portion affected glomerulus may be sclerosed. Although diagnosis based on microscopic features, patient stratification relies clinical data such as proteinuria etiological criteria. FSGS affects both children adults has an elevated risk progression to end-stage renal disease. The prevalence rising among various populations, efficacy therapies limited. Therefore, understanding pathophysiology developing targeted address complex needs patients topics great interest currently being studied across trials. We discuss etiology FSGS, describe major contributing pathophysiological pathways, outline emerging therapeutic strategies along with their pitfalls.

Язык: Английский

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Post-operative recurrence of focal segmental glomerulosclerosis according to pre-transplant treatment after kidney transplantation

BMC Nephrology, Год журнала: 2023, Номер 24(1)

Опубликована: Март 15, 2023

Abstract Background Recurrent focal segmental glomerulosclerosis (FSGS) after kidney transplantation (KT) is a serious complication and significant risk factor for graft failure. However, there no clear evidence of the effectiveness pre-transplant treatment using plasmapheresis (PP) or rituximab in preventing post-operative FSGS recurrence KT. Methods This single-center retrospective study included 99 adult patients with biopsy-proven primary who underwent KT between 2007 2018. The were divided into pre-treatment group (N = 53, 53.5%) 46, 46.5%). In group, prophylactic PP was administered before undergoing living donor day those deceased transplantation. Results rate immediate significantly higher (16 [34.8%]) than (5 [9.4%]; P 0.002). There three cases failure due to recurrent FSGS, all which group. After adjusting possible confounding factors, age (per 10-year increase; OR 0.61, CI, 0.42–0.90; 0.012) (vs. treatment; 0.17, 0.05–0.54; 0.003) identified as factors associated recurrence. death-censored survival superior pretransplant ( 0.042). Conclusion Pre-transplant beneficial effects on

Язык: Английский

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A Rare Case of Donor-Derived Renal Cell Carcinoma in a Kidney Transplant Recipient

American Journal of Case Reports, Год журнала: 2024, Номер 25

Опубликована: Янв. 18, 2024

BACKGROUND:The incidence of renal cell carcinoma (RCC) in transplanted kidneys is reported to be about 0.2%, which makes this case exceedingly rare. Risk factors include older age the donors, smoking, obesity, and hypertension. Higher incidences allograft RCC have been seen patients who received a kidney from deceased donor rather than living donor. CASE REPORT:A 71-year-old woman with end-stage disease underwent transplantation (DDKT) 1 year before presentation. The immune-suppressive regimen was Envarsus, Myfortic, prednisone. Allograft functioned baseline creatinine 1.4-1.5 mg/dL. patient presented due recurring UTIs, prompted ultrasound that showed mass on allograft. Abdominal MRI demonstrated 3.5-cm upper pole. Biopsy clear-cell RCC, Fuhrman nuclear grade 3. partial nephrectomy. Following nephrectomy, serum 1.7-2 discharged immunosuppressive therapy consisting prednisone, Rapamune after diagnosis. CONCLUSIONS:There are no standard treatment guidelines or optimal immune for management transplant recipients. Options radical nephron-sparing surgery (NSS), radiofrequency ablation (RFA), active surveillance. According systematic review, recurrence cancer nephrectomy 3.6% 3.1 years, similar non-transplanted kidneys. There not enough evidence support screening kidneys, but constitutional symptoms like recurrent UTIs should prompt further investigation potential malignancies these patients.

Язык: Английский

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Management and long-term outcome of recurrent idiopathic FSGS in pediatric kidney transplant recipients

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Окт. 26, 2024

Focal segmental glomerulosclerosis (FSGS) is a major cause of pediatric kidney failure. Most cases FSGS in children are idiopathic and have high risk post-transplantation recurrence graft loss. Common treatments for recurrent (rFSGS) include plasmapheresis, immunoadsorption, and/or immunomodulatory therapy. This study retrospectively evaluated the efficacy safety early plasmapheresis followed by rituximab inducing maintaining remission rFSGS. Between 2014 2023, 8 65 transplant recipients at our center were diagnosed with FSGS. rFSGS was based on nephrotic range proteinuria no other managed plasmapheresis. Rituximab therapy used those who did not achieve complete prolonged or remained dependent. 6 (75%) experienced All patients achieved partial response times ranging from to 379 days (median 13 days). introduced 5 plasmapheresis-dependent patients, leading sustained cessation 3 while 2 showed improved reduced frequency. Adverse effects included rituximab-induced serum sickness one patient mild allergic reaction. One loss due humoral rejection, but grafts lost rFSGS, all functional over an average follow-up 50 months. Early effectively induces most cases, well tolerated, prevents Larger studies needed confirm these findings.

Язык: Английский

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FSGS Recurrence Collaboration: Report of a Symposium

Glomerular Diseases, Год журнала: 2023, Номер 4(1), С. 1 - 10

Опубликована: Ноя. 14, 2023

Since it was first described more than 50 years ago, recurrence of FSGS in kidney allografts has frustrated the transplant community. This rare condition is associated with considerable morbidity, and most common cause graft loss patients CKD stage 5 due to FSGS. However, problem remains insufficiently studied. It an ultra-orphan disease incidence rates at individual centers are often very low unpredictable. The published literature contains conflicting reports basic epidemiologic data. Progress defining mechanisms advancing therapeutic options been limited. treatment that currently available limited largely ineffective. range time variability responsiveness suggest not a single entity, but rather multiple phenotypes resulting from diverse pathogenetic grouped under larger umbrella. There urgent need for innovative science translational research [1] better understand mechanistic perspective; [2] improve risk stratification predict this outcome; [3] develop effective therapies. In conference report, we describe work investigators whose state-of-the-art paves way approaches diagnosis provides hope can achieve these objectives affected patients.

Язык: Английский

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Pemphigus vulgaris and focal segmental glomerulosclerosis (FSGS): First reported case and a review of the literature

Clinical Case Reports, Год журнала: 2023, Номер 11(7)

Опубликована: Июль 1, 2023

There may be a connection between pemphigus vulgaris and nephrotic syndrome, as evidenced by the occurrence of focal segmental glomerulosclerosis in our patient reviewing relevant literature. Therefore, if with presents bilateral lower extremity edema or proteinuria detected during urinalysis, it could indicate involvement kidneys.

Язык: Английский

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Strategies for choosing the best living donor: A review of the literature and a proposal of a decision‐making paradigm

Pediatric Transplantation, Год журнала: 2024, Номер 28(4)

Опубликована: Май 20, 2024

Abstract Transplantation remains the gold‐standard treatment for pediatric end‐stage kidney disease. While living donor transplant is preferred option most patients, it not right choice all. For those who have to choose between deceased and transplantation, or from among multiple potential donors, clinician must weigh dynamic factors identify optimal donor. This review will cover key considerations when choosing donors propose a decision‐making algorithm.

Язык: Английский

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Assessment of podocyte detachment as a pivotal step in the development of focal segmental glomerulosclerosis

Journal of the Egyptian National Cancer Institute, Год журнала: 2024, Номер 36(1)

Опубликована: Ноя. 18, 2024

Abstract Background Podocytopenia refers to a decrease in the number of podocytes. When podocytes are injured, they may detach leading podocytopenia, which represents critical step development podocytopathy and subsequently deterioration renal functions. Pathological assessment podocytopenia plays crucial role diagnosing underlying kidney diseases. Aim To assess detached evaluate their diagnostic focal segmental glomerulosclerosis. Materials methods This is retrospective study, conducted on 67 archival biopsies with clinical diagnosis steroid-resistant or steroid-dependent nephrotic syndrome (SRNS) diagnosed as glomerulosclerosis (FSGS) by electron microscopy (EM). Colloidal iron stain Desmin immunohistochemical were performed. Assessment mean percent stained pixels relation surface tuft area glomerulus, i.e., (PSA) was done using image analysis system (ImageJ 1.52a) software. Results Podocytopathy 35 (52.24%) cases, while FSGS 32 (47.76%) cases. Regarding podocytes, 27 (49.3%) cases showed no light (LM), only 4 (6%) severe podocyte detachment. There statistically significant difference between control both regarding PSA ( p ≤ 0.001). Conclusion Standardized reporting cells becoming mandatory have high positive predictive value for expected EM picture.

Язык: Английский

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