Urinary apolipoprotein AI in children with kidney disease

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

“…Moreover, data of a follow-up study of primary FSGS patients from before to one year after kidney transplantation has shown that all the patients that did not recur were ApoA-Ib negative before and after kidney transplantation (n = 9), and in the relapsing FSGS patients (n = 4) ApoA-Ib predated the FSGS recurrence event in 3 out of 4 studied cases, in two cases even before transplantation 8 . Our findings are further supported by an independent study that demonstrated an increase of high molecular weight forms of ApoA-I in the urine of pediatric patients with relapsing FSGS 9 , confirming the relationship of modified forms of ApoA-I and FSGS 10 .…”

“…In our seminal study we described that not only ApoA-Ib, but also other less abundant low MW forms of ApoA-I were detected in urine of recurrent FSGS patients 7 . Clark A. and collaborators have recently found high MW forms of ApoA-I in urine of paediatric FSGS patients in relapse 9 , a fact that reinforces the idea that Apo-AI and/or modifications on this lipoprotein may have a role in FSGS development 10 . We have not considered these higher molecular weight forms of ApoA-I because they were not previously detected in our initial proteomic discovery phase without targeting specifically for ApoA-I 7 .…”

“…Urinary ApoA-Ib, a high molecular weight form of ApoA-I discovered by our group, has proven to be specifically related to idiopathic FSGS recurrence after kidney transplantation 7,8 . Likewise, an independent study in paediatric patients has also detected the presence of heavy forms of ApoA-I in urine of patients with relapsing FSGS in native kidneys 9 , reinforcing the idea that modifications in the ApoA-I structure could be involved in the FSGS pathogenesis 10 . Unravelling the structure of ApoA-Ib could shed light on the understanding of the pathological mechanisms of idiopathic FSGS which still remain an unsettled issue 28 .…”

“…The molecular mass of proApoA-I (28.9 kDa) is similar to the expected mass of ApoA-Ib but with a more basic isoelectric point (IEP) (5.45 vs ≈ 5.27) 16,17 and thus widely separated in two dimensional gels. Finally, forms of ApoA-I around 50 kDa have been detected in blood related to cardiovascular disease events 24,25 and also in urine of pediatric FSGS patients 9 . The origin of this 50 kDa variants is unclear but its molecular mass and electrophoretic properties certainly differ from ApoA-Ib 9,26,27 .…”

Challenges in primary focal segmental glomerulosclerosis diagnosis: from the diagnostic algorithm to novel biomarkers

“…ApoA-Ib also has a potential prognostic value, as it can be found in urine before the FSGS recurrence episodes [ 10 ]. Although the exact role of apoA-Ib in FSGS is unknown, other authors have also found increased levels of apoA-I [ 108 ] or the presence of high molecular weight forms of apoA-I [ 109 ] in urine of FSGS patients, reinforcing the idea that either apoA-I or the mechanisms that modify this lipoprotein are involved in the pathogenic mechanism of this disease [ 110 ]. The potential role of this biomarker to discriminate primary FSGS in native kidney is currently being pursued, but preliminary results obtained with idiopathic FSGS patients before kidney transplantation pointed out that the detection of apoA-Ib in native kidney patients is associated with a worse prognosis [ 10 ].…”