A Specific Tubular ApoA-I Distribution Is Associated to FSGS Recurrence after Kidney Transplantation
Abstract
:1. Introduction
2. Experimental Section
2.1. Patients and Samples
2.2. Urinary ApoA-Ib Detection
2.3. Histological Analysis
2.4. Immunodetection of ApoA-I in Renal Biopsies
3. Results
3.1. Demographic and Baseline Characteristics
3.2. ApoA-I Is Located on the Brush Border of the Tubular Cells of FSGS Recurrent Patients
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Ponticelli, C. Recurrence of focal segmental glomerular sclerosis (FSGS) after renal transplantation. Nephrol. Dial. Transplant. 2010, 25, 25–31. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rosenberg, A.Z.; Kopp, J.B. Focal Segmental Glomerulosclerosis. Clin. J. Am. Soc. Nephrol. 2017, 12, 502–517. [Google Scholar] [CrossRef] [Green Version]
- Sprangers, B.; Kuypers, D.R. Recurrence of glomerulonephritis after renal transplantation. Transplant. Rev. 2013, 27, 126–134. [Google Scholar] [CrossRef] [PubMed]
- Lopez-Hellin, J.; Cantarell, C.; Jimeno, L.; Sanchez-Fructuoso, A.; Puig-Gay, N.; Guirado, L.; Vilariño, N.; Gonzalez-Roncero, F.M.; Mazuecos, A.; Lauzurica, R.; et al. A form of apolipoprotein a-I is found specifically in relapses of focal segmental glomerulosclerosis following transplantation. Am. J. Transplant 2013, 13, 493–500. [Google Scholar] [CrossRef] [PubMed]
- Puig-Gay, N.; Jacobs-Cacha, C.; Sellarès, J.; Guirado, L.; González Roncero, F.; Jiménez, C.; Zárraga, S.; Paul, J.; Lauzurica, R.; Alonso, Á.; et al. Apolipoprotein A-Ib as a biomarker of focal segmental glomerulosclerosis recurrence after kidney transplantation: Diagnostic performance and assessment of its prognostic value—A multi-centre cohort study. Transpl. Int. 2019, 32, 313–322. [Google Scholar] [CrossRef]
- Clark, A.J.; Jabs, K.; Hunley, T.E.; Jones, D.P.; VanDeVoorde, R.G.; Anderson, C.; Du, L.; Zhong, J.; Fogo, A.B.; Yang, H.; et al. Urinary apolipoprotein AI in children with kidney disease. Pediatr. Nephrol. 2019, 34, 2351–2360. [Google Scholar] [CrossRef]
- Clark, A.J.; Yang, H.; Kon, V. Urinary apoAl: Novel marker of renal disease? Pediatr. Nephrol. 2019, 34, 2425–2426. [Google Scholar] [CrossRef]
- Jacobs-Cachá, C.; López-Hellín, J. Should high molecular weight forms of apolipoprotein A-I be analyzed in urine of relapsing FSGS patients? Pediatr. Nephrol. 2019, 34, 2423–2424. [Google Scholar] [CrossRef]
- Meyer, T.W. Tubular injury in glomerular disease. Kidney Int. 2003, 63, 774–787. [Google Scholar] [CrossRef] [Green Version]
- Singh, P.; Thomson, S.C. Renal homeostasis and tubuloglomerular feedback. Curr. Opin. Nephrol. Hypertens. 2010, 19, 59–64. [Google Scholar] [CrossRef]
- Erkan, E.; Garcia, C.D.; Patterson, L.T.; Mishra, J.; Mitsnefes, M.M.; Kaskel, F.J.; Devarajan, P. Induction of renal tubular cell apoptosis in focal segmental glomerulosclerosis: Roles of proteinuria and Fas-dependent pathways. J. Am. Soc. Nephrol. 2005, 16, 398–407. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Abbate, M.; Zoja, C.; Remuzzi, G. How Does Proteinuria Cause Progressive Renal Damage? J. Am. Soc. Nephrol. 2006, 17, 2974–2984. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wu, X.; He, Y.; Jing, Y.; Li, K.; Zhang, J. Albumin overload induces apoptosis in renal tubular epithelial cells through a CHOP-dependent pathway. Omi. A J. Integr. Biol. 2010, 14, 61–73. [Google Scholar] [CrossRef] [PubMed]
- Ohse, T.; Inagi, R.; Tanaka, T.; Ota, T.; Miyata, T.; Kojima, I.; Ingelfinger, J.R.; Ogawa, S.; Fujita, T.; Nangaku, M. Albumin induces endoplasmic reticulum stress and apoptosis in renal proximal tubular cells. Kidney Int. 2006, 70, 1447–1455. [Google Scholar] [CrossRef] [Green Version]
- Zoja, C.; Abbate, M.; Remuzzi, G. Progression of renal injury toward interstitial inflammation and glomerular sclerosis is dependent on abnormal protein filtration. Nephrol. Dial. Transplant. 2015, 30, 706–712. [Google Scholar] [CrossRef] [Green Version]
- Cameron, J.S. Proteinuria and progression in human glomerular diseases. Am. J. Nephrol. 1990, 10, 81–87. [Google Scholar] [CrossRef]
- Troost, J.P.; Trachtman, H.; Spino, C.; Kaskel, F.J.; Friedman, A.; Moxey-Mims, M.M.; Fine, R.N.; Gassman, J.J.; Kopp, J.B.; Walsh, L.; et al. Proteinuria Reduction and Kidney Survival in Focal Segmental Glomerulosclerosis. Am. J. Kidney Dis. 2020. [Google Scholar] [CrossRef]
- Bu, L.; Mirocha, J.; Haas, M. Immunoglobulin G/albumin staining in tubular protein reabsorption droplets in minimal change disease and focal segmental glomerulosclerosis. Nephrol. Dial. Transplant. 2020. [Google Scholar] [CrossRef]
- Hammad, S.M.; Barth, J.L.; Knaak, C.; Argraves, W.S. Megalin acts in concert with cubilin to mediate endocytosis of high density lipoproteins. J. Biol. Chem. 2000, 275, 12003–12008. [Google Scholar] [CrossRef] [Green Version]
- Aseem, O.; Smith, B.T.; Cooley, M.A.; Wilkerson, B.A.; Argraves, K.M.; Remaley, A.T.; Argraves, W.S. Cubilin Maintains Blood Levels of HDL and Albumin. J. Am. Soc. Nephrol. 2014, 25, 1028–1036. [Google Scholar] [CrossRef] [Green Version]
- Jacobs-Cachá, C.; Puig-Gay, N.; Helm, D.; Rettel, M.; Sellarès, J.; Meseguer, A.; Savitski, M.M.; Moreso, F.J.; Soler, M.J.; Seron, D.; et al. A misprocessed form of Apolipoprotein A-I is specifically associated with recurrent Focal Segmental Glomerulosclerosis. Sci. Rep. 2020, 10, 1159. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jacobs-Cachá, C.; Vergara, A.; García-Carro, C.; Agraz, I.; Toapanta-Gaibor, N.; Ariceta, G.; Moreso, F.; Serón, D.; López-Hellín, J.; Soler, M.J. Challenges in primary focal segmental glomerulosclerosis diagnosis: From the diagnostic algorithm to novel biomarkers. Clin. Kidney J. 2020. [Google Scholar] [CrossRef] [PubMed]
Histology | |||||||||||||
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Patient | Gender | Age (Years) | Native Kidney Disease | Transplant Number | Biopsy Indication | Time after KT (Years) | Proteinuria (g/24 h) | Serum Albumin (g/dL) | Serum Creatinine (mg/dL) | Light Microscopy | Electronic Microscopy | Urinary ApoA-Ib | |
FSGS recurrence | 1 | male | 48 | Primary FSGS | First | Proteinuria | 1.67 | 4.1 | 4.26 | 2.18 | FSGS | - * | Positive |
2 | male | 53 | Primary FSGS | First | Proteinuria | 0.75 | 9.6 | 3.32 | 1.86 | IFTA II | >80% foot process effacement | Positive | |
3 | female | 32 | Primary FSGS | First | Proteinuria | 0.60 | 1.2 | 3.4 | 1.62 | IFTA II/Borderline rejection | >80% foot process effacement | Positive | |
4 | female | 75 | Primary FSGS | First | Proteinuria | 0.06 (21 days) | 2 | 3.92 | 2.46 | FSGS/IFTA I | >80% foot process effacement | Positive | |
Non-FSGS | 5 | male | 27 | MPGN | First | Graft dysfunction | 0.21 | 0.5 | 4.6 | 1.46 | Acute cellular rejection IA/IFTA I | - | Negative |
6 | male | 49 | Unknown cause of ESRD | Second | Delayed graft function | 0.03 (10 days) | 1 | 4.2 | 2.42 | Borderline rejection | - | Negative | |
7 | male | 45 | Unknown cause of ESRD | First | Graft dysfunction /proteinuria | 2.99 | 1.8 | 3.9 | 2.01 | Chronic humoral rejection/Borderline rejection/ Arteriolar hyalinosis/IFTA II | - | Negative | |
8 | male | 39 | ESRD secondary to congenital kidney hypoplasia | Fourth | Surveillance | 0.36 | 0.9 | 4.4 | 1.25 | Acute humoral rejection | - | Negative |
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Jacobs-Cachá, C.; Puig-Gay, N.; Vergara, A.; Gabaldon, M.-A.; Sellarés, J.; Villena-Ortiz, Y.; Agraz, I.; Moreso, F.; Soler, M.J.; Serón, D.; et al. A Specific Tubular ApoA-I Distribution Is Associated to FSGS Recurrence after Kidney Transplantation. J. Clin. Med. 2021, 10, 2174. https://doi.org/10.3390/jcm10102174
Jacobs-Cachá C, Puig-Gay N, Vergara A, Gabaldon M-A, Sellarés J, Villena-Ortiz Y, Agraz I, Moreso F, Soler MJ, Serón D, et al. A Specific Tubular ApoA-I Distribution Is Associated to FSGS Recurrence after Kidney Transplantation. Journal of Clinical Medicine. 2021; 10(10):2174. https://doi.org/10.3390/jcm10102174
Chicago/Turabian StyleJacobs-Cachá, Conxita, Natàlia Puig-Gay, Ander Vergara, Maria-Alejandra Gabaldon, Joana Sellarés, Yolanda Villena-Ortiz, Irene Agraz, Francesc Moreso, Maria José Soler, Daniel Serón, and et al. 2021. "A Specific Tubular ApoA-I Distribution Is Associated to FSGS Recurrence after Kidney Transplantation" Journal of Clinical Medicine 10, no. 10: 2174. https://doi.org/10.3390/jcm10102174