Apolipoprotein A-Ib as Biomarker of FSGS Recurrence After Kidney Transplantation: Diagnostic Performance in a Prospective Cohort and Assessment of its Prognostic Value
Conxita Jacobs Cachá2,18, Natalia Puig Gay18, Joana Sellares1,2, Lluis Guirado3, Francisco Gonzalez Roncero4, Carlos Jimenez5, Sofia Zárraga6, Javier Paul7, Lauzurica Ricardo8, Angel Alonso9, Fernandez Ana10, Beneyto Isabel11, Mazuecos Auxiliadora12, Hernandez Domingo13, Rodriguez-Benot Alberto14, Antonio Franco15, Jimeno Luisa16, Marta Crespo17, Anna Meseguer18, Francesc Moreso1,2, Daniel Seron1,2, Joan López Hellín18, Carmen Cantarell 2.
1Nephrology , Vall d'Herbón Hospital, Barcelona, Spain; 2Nephrology Group, Vall d'Hebron Research Institute, Barcelona, Spain; 3Nephrology , Fundacio Puigvert, Barcelona, Spain; 4Nephrology , Hospital Virgen del Rocio, Sevilla, Spain; 5Nephrology , Hospital Universitario La Paz, Madrid, Spain; 6Nephrology , Hospital de Cruces, Barakaldo, Spain; 7Nephrology , Hospital Miguel Servet, Zaragoza, Spain; 8Nephrology , Hospital Germans Trias i Pujol, Barcelona, Spain; 9Nephrology , Hospital Universitario de A Coruña, A Coruña, Spain; 10Nephrology , Hospital Ramon y Cajal, Madrid, Spain; 11Nephrology , Hospital Universitari i Politecnic La Fe, Valencia, Spain; 12Nephrology , Hospital Puerta del Mar, Cadiz, Spain; 13Nephrology , Hospital Carlos Haya, Malaga, Spain; 14Nephrology , Hospital Reina Sofia, Cordoba, Spain; 15Nephrology , Hospital General , Alicante, Spain; 16Nephrology , Hospital Virgen de Arrixaca, Murcia, Spain; 17Nephrology , Hospital del Mar, Barcelona, Spain; 18Kidney Pathophysiology Group, Vall d'Hebron Research Institute, Barcelona, Spain
Grupo Español de actualización en Transplante (GREAT).
Background: Recurrence of idiopathic FSGS is a serious complication after kidney transplantation. Currently, there are no accurate means to diagnose the relapses or to detect the patients at risk. In a previous study we detected Apolipoprotein A-Ib (ApoA-Ib) specifically in urine of kidney transplanted patients that showed recurrence of FSGS. In the present work we aim to confirm the diagnostic performance of ApoA-Ib to detect FSGS recurrence and assess its possible prognostic value.
Methods: Between January 2013 and December 2015 a urine sample was obtained in three groups of kidney transplant patients treated at the nephrology department of 16 major Spanish hospitals: FSGS patients that relapsed after kidney transplantation (FSGS-R), FSGS patients that did not show recurrence after kidney transplantation (FSGS-NR) and non-FSGS kidney transplanted patients (No-FSGS). ApoA-Ib was determined in the urine of these patients by immunodetection. To assess the ApoA-Ib predictive ability of detecting patients at risk of relapse, 33 patients with idiopatic FSGS were included before transplantation. Thirteen of them were transplanted and followed up to 1 year after transplantation. In these patients ApoA-Ib was periodically determined.
Results: In the FSGS-R group 14 out of 15 (93.3 %) were positive for apoA-Ib whereas only 2 out of 22 (9.1 %) in the FSGS-NR group and 3 out of 24 (12.5 %) in the No-FSGS group tested positive for ApoA-Ib (P value < 0.001). ApoA-Ib sensitivity and specificity to detect FSGS recurrence were 94.1% and 90.9% to discriminate non-relapsing FSGS patients or 94.1% and 87.5% to discriminate transplanted patients without FSGS as the primary disease. These results were consistent with the obtained in our previous cohort of FSGS patients. The presence of ApoA-Ib in urine was only related to FSGS recurrence and was independent of proteinuria levels or renal function. ApoA-Ib was present in 37.9 % of the FSGS patients before transplantation which is similar to the FSGS recurrence incidence after transplantation (30-50 %). Four of the 13 followed patients showed FSGS recurrence. ApoA-Ib predated FSGS relapse in 4 out of 5 recurrence episodes observed in 4 patients, while in 9 patients who did not relapse ApoA-Ib was negative in 37 out of 38 samples.
Conclusions: ApoA-Ib has the potential to be a good complementary diagnostic biomarker of FSGS relapses after transplantation, providing a confident exclusion of relapse even in the presence of high proteinuria. It has also a potential to detect patients at risk of relapse, even before transplantation, which should be further evaluated in a larger cohort.
The authors thank Oreto Prat, Estefanía Lozano and Anna Caraben for their technical assistance. Grupo Español de Actualización en Trasplante (GREAT, Spanish Group for New Projects in Transplantation): Carme Cantarell (Hospital Vall d’Hebron, Barcelona), Lluis Guirado (Fundació Puigvert, Barcelona), Francisco Gonzalez Roncero (Hospital Virgen del Rocio, Sevilla), Juan C. Ruiz San Millan (Hospital Marqués de Valdecilla, Santander) Carlos Jiménez (Hospital Universitario La Paz, Madrid), Isabel Beneyto (Hospital La Fe, Valencia), Sofia Zárraga (Hospital de Cruces, Barakaldo), Javier Paul (Hospital Miguel Servet, Zaragoza), Vicenç Torregrosa (Hospital Clínic, Barcelona), Ricardo Lauzurica (Hospital Germans Trias i Pujol, Badalona), Angel Alonso (Hospital de A Coruña, A Coruña), Carmen Díaz (Hospital Central de Asturias, Oviedo), Ana Fernández (Hospital Ramón y Cajal, Madrid), Auxiliadora Mazuecos (Hospital Puerta del Mar, Cadiz), Domingo Hernández (Hospital Carlos Haya, Malaga), Alberto Rodriguez (Hospital Reina Sofia, Cordoba), Antonio Osuna (Hospital Virgen de las Nieves, Granada), Antonio Franco (Hospital General, Alicante), Luisa Jimeno (Hospital Virgen de la Arrixaca, Murcia), Marta Crespo (Hospital del Mar, Barcelona)..
