Delineating the Picture of Renal Graft Injury in 2011

Abstract

To the Editor: We read with great interest this recent article entitled ‘The histology of Solitary Renal Allograft at 1 and 5 Years After Transplantation’ (1Stegall MD Park WD Larson TS et al.The histology of solitary renal allografts at 1 and 5 years after transplantation.Am J Transplant. 2011; 11: 698-707Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar) published in AJT. In this paper, the authors show a dramatic reduction in renal allograft scarring lesions in the 5 years posttransplant, with moderate to severe fibrosis of 13% and 17% at 1 year and 5 years after transplantation, respectively, as compared to the results previously obtained by other groups (2Nankivell BJ Borrows RJ Fung CL O’Connell PJ Allen RD Chapman JR The natural history of chronic allograft nephropathy.N Engl J Med. 2003; 349: 2326-2333Crossref PubMed Scopus (1668) Google Scholar, 3Tantravahi J Womer KL Kaplan B Why hasn’t eliminating acute rejection improved graft survival?.Annu Rev Med. 2007; 58: 369-385Crossref PubMed Scopus (75) Google Scholar, 4Schwarz A Mengel M Gwinner W et al.Risk factors for chronic allograft nephropathy after renal transplantation: A protocol biopsy study.Kidney Int. 2005; 67: 341-348Abstract Full Text Full Text PDF PubMed Scopus (168) Google Scholar) including ours (5Legendre C Thervet E Skhiri H et al.Histologic features of chronic allograft nephropathy revealed by protocol biopsies in kidney transplant recipients.Transplantation. 1998; 65: 1506-1509Crossref PubMed Scopus (148) Google Scholar). Based on these findings, the authors suggest a ‘revised concept of histologic injury in which moderate-to-severe fibrosis and hyalinosis may be avoided in the majority of renal allografts in the first 5 years after transplantation’. We believe that this study, using a substantial number of protocol biopsies is relevant and improves our understanding of chronic allograft damage progression (2Nankivell BJ Borrows RJ Fung CL O’Connell PJ Allen RD Chapman JR The natural history of chronic allograft nephropathy.N Engl J Med. 2003; 349: 2326-2333Crossref PubMed Scopus (1668) Google Scholar), but should be interpreted with caution. In particular, the applicability of these results in nonselected populations of kidney transplant recipients (KTR) may not be valid since the study focuses on a highly selected population of stable KTR, mostly living donors, with low immunological risk and transplanted with a mean donor age of 41 years [below the average value obtained in Europe (6Agence de la Biomedecine Annual Report. Available at: http://www.agence-biomedecine.fr. Accessed April 2011.Google Scholar)]. Importantly, some methodological issues seem to be problematic: (i) first, the authors exclude from the analysis 219 patients who either lost function or were lost to follow-up before 5 years (flow chart, Figure 1). In a further analysis (supplementary Table 4), they claim that these groups of patients present similar chronicity Banff levels at 1 year (with the exception of cg) as compared to the 518 patients who reached 5 years. Of note, this analysis has been performed on only 107 of the 219 patients (49%) who did not reach 5 years, which may represent a bias in the group comparison. (ii) Second, the multivariate model may present potential weakness: the authors use in their model the variable ‘any complications’ mixing immunological with nonimmunological factors and containing variables that may not be independent [e.g., acute rejection and delayed graft function (2Nankivell BJ Borrows RJ Fung CL O’Connell PJ Allen RD Chapman JR The natural history of chronic allograft nephropathy.N Engl J Med. 2003; 349: 2326-2333Crossref PubMed Scopus (1668) Google Scholar) table 5]. Moreover, transplant glomerulopathy (cg) is used twice in the multivariate model: cg is part of the variable ‘1–5 years any complications’ and is also used in the 1 year chronicity score, which is methodologically not optimal. Finally, we believe, that the authors convincingly demonstrate the concept that stable kidneys with low immunological risk and from living donors reaching 5 years posttransplant have low chronicity scores, which is relevant information, but addresses only one part of the question. The next step would be to extend such analysis to large data sets of protocol biopsies of nonselected population of kidney recipients and importantly including the patients at risk that lose their kidney before 5 years. Such analysis would permit to assess the ‘overall’ picture of graft injury in 2011 and importantly the respective impacts represented by specific diseases such as ABMR, TCMR, disease recurrence in the process that contributes to chronic-allograft-damage represented by cv, cg, IFTA and ah lesions. The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.