A misprocessed form of Apolipoprotein A-I is specifically associated with recurrent Focal Segmental Glomerulosclerosis

Jacobs-Cachá, Conxita; Puig-Gay, Natàlia; Helm, Dominic; Rettel, Mandy; Sellarès, Joana; Meseguer, Anna; Savitski, Mikhail M.; Moreso, Francesc; Serón, Daniel; López-Hellı́n, Joan

doi:10.1038/s41598-020-58197-y

Cited by 15 publications

(14 citation statements)

References 47 publications

(62 reference statements)

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“…A younger age at diagnosis, severe hypoalbuminaemia and rapid progression to ESKD (for example, within 3 years of diagnosis) are also more common in patients who experience recurrence after transplantation. Apolipoprotein A-Ib, a high-molecular-weight form of apolipoprotein A-I, was recently proposed as a possible biomarker for recurrent forms of podocytopathies after kidney transplantation 224 . Typically, relapses occur in the first 2 weeks after kidney transplantation and often respond to combined treatment with plasma exchange, rituximab and intensified immunosuppression, although the response may be transient 225,226 .…”

Section: Relapse After Transplantationmentioning

confidence: 99%

Podocytopathies

Kopp

Anders

Suszták

et al. 2020

Nat Rev Dis Primers

307

270

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Podocytopathies are kidney diseases in which direct or indirect podocyte injury drives proteinuria or nephrotic syndrome. In children and young adults, genetic variants in >50 podocyte-expressed genes, syndromal non-podocyte-specific genes and phenocopies with other underlying genetic abnormalities cause podocytopathies associated with steroid-resistant nephrotic syndrome or severe proteinuria. A variety of genetic variants likely contribute to disease development. Among genes with non-Mendelian inheritance, variants in APOL1 have the largest effect size. In addition to genetic variants, environmental triggers such as immune-related, infection-related, toxic and haemodynamic factors and obesity are also important causes of podocyte injury and frequently combine to cause various degrees of proteinuria in children and adults. Typical manifestations on kidney biopsy are minimal change lesions and focal segmental glomerulosclerosis lesions. Standard treatment for primary podocytopathies manifesting with focal segmental glomerulosclerosis lesions includes glucocorticoids and other immunosuppressive drugs; individuals not responding with a resolution of proteinuria have a poor renal prognosis. Renin-angiotensin system antagonists help to control proteinuria and slow the progression of fibrosis. Symptomatic management may include the use of diuretics, statins, infection prophylaxis and anticoagulation. This Primer discusses a shift in paradigm from patient stratification based on kidney biopsy findings towards personalized management based on clinical, morphological and genetic data as well as pathophysiological understanding.

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Section: Relapse After Transplantationmentioning

confidence: 99%

Podocytopathies

Kopp

Anders

Suszták

et al. 2020

Nat Rev Dis Primers

307

270

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“…Amongst the several modified ApoA-I forms, ApoA-1b is noted to be present in the urine of recurrent FSGS. ApoA-Ib is a high molecular weight form of ApoA-I that may be associated with a misprocessed form of ApoA-I precursor with no genetic variations in the ApoA-I gene [31]. One study performed a proteomic analysis of serum and urine samples of transplant patients with history of primary FSGS; the results showed the existence of ApoA-Ib exclusively in patients with relapsing FSGS [29].…”

Section: Circulating Permeability Factors Of Fsgsmentioning

confidence: 99%

Update on Recurrent Focal Segmental Glomerulosclerosis in Kidney Transplantation

Shoji

Mii

Terasaki

et al. 2020

Nephron

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Background: Focal segmental glomerulosclerosis (FSGS) is a clinicopathological syndrome characterized by nephrotic-range proteinuria with high incidence of progression to end-stage renal disease (ESRD). In primary FSGS, 40–60% of patients develop ESRD within 10–20 years. Summary: Recurrence of FSGS after kidney transplantation is frequent and is associated with poor allograft survival. The risk factors for recurrent FSGS include onset of FSGS during childhood, rapid progression of primary FSGS to ESRD, history of recurrent FSGS in previous allograft, and diffuse mesangial hypercellularity or collapsing variant of FSGS in the native kidney. The early histological findings of recurrent FSGS consist of unremarkable glomerular changes on light microscopy but significant podocyte effacement on electron microscopy; the loss of foot processes with eventual dropout of podocytes leads to the development of segmental lesions in the glomerulus. Experimental and clinical data suggest the existence of circulating permeability factors, such as soluble urokinase-type plasminogen activator receptor (suPAR), cardiotrophin-like cytokine factor-1 (CLCF-1), CD40 axis, and apolipoprotein A-Ib (ApoA-Ib), in the pathogenesis of recurrent FSGS. These biomarkers including circulating permeability factors may facilitate earlier diagnosis of FSGS posttransplant and may guide in the development of novel therapies that may be more effective and improve long-term outcomes in kidney transplantation. Key Messages: Several studies have suggested the possible circulating permeability factors, such as suPAR, CLCF-1, CD40 axis, and ApoA-Ib, in the pathogenesis and disease progression of FSGS and recurrent FSGS. Further studies should be performed to elucidate the true essential biomarker(s) associated with the onset and progression of FSGS as well as recurrent FSGS.

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“…Most recurrences occur early with a median time of 1.5-12 months in primary FSGS [37 && ,45]. The early and high recurrence rates of primary FSGS has been attributed to the presence of a circulating permeability factor in the sera of KTRs, the identity of which has been the subject of ongoing research [42,46]. Savin et al [47] first demonstrated that rats exposed to sera of patients with recurrent FSGS developed albuminuria, while Gallon et al [48] later described a case of rapidly recurrent FSGS in a living donor recipient in which there was a reversal of the histopathologic and clinical features of FSGS in the same allograft after it was explanted and retransplanted into a different recipient without native FSGS.…”

Section: Focal and Segmental Glomerulosclerosismentioning

confidence: 99%

Recurrent glomerulonephritis after renal transplantation

Chukwu

Middleton

Kalra

2020

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of reviewThe current understanding of the incidence, predisposing factors, pathophysiology and effective treatment of recurrent glomerulonephritis (RGN) in renal transplants remains at best patchy and at worst, completely lacking. Current reports have been limited by inconsistencies in study design, sample populations and lengths of follow-up. Making sense of the available evidence will provide the tools to support transplant nephrologists in their management of allograft donors and recipients. Recent findingsWith better survival of renal allografts, RGN has become a dominant factor influencing allograft survival. Evidently, the risk of recurrence is proportional to the incremental time posttransplantation. The proposed risk factors for RGN include but are not limited to the severity of primary glomerulonephritis (PGN), younger recipient age, live-related donor allograft, minimal HLA mismatch, steroid avoidance and nonuse of induction therapy. Unfortunately, these findings are derived from retrospective cohort and registry studies; hence, true causality for RGN is hard to prove.

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A misprocessed form of Apolipoprotein A-I is specifically associated with recurrent Focal Segmental Glomerulosclerosis

Cited by 15 publications

References 47 publications

Podocytopathies

Podocytopathies

Update on Recurrent Focal Segmental Glomerulosclerosis in Kidney Transplantation

Recurrent glomerulonephritis after renal transplantation

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