LETTER TO THE EDITOR
Year : 2011 | Volume
: 22 | Issue : 6 | Page : 1261--1262
Antibody-mediated rejection: Importance of lactate dehydrogenase and neutrophilia in early diagnosis
Muhammed Mubarak1, Khawar Abbas2,
1 Department of Histopathology, Sindh Institute of Urology and Transplantation, Karachi - 74200, Pakistan
2 Department of Immunology, Sindh Institute of Urology and Transplantation, Karachi - 74200, Pakistan
Department of Histopathology, Sindh Institute of Urology and Transplantation, Karachi - 74200
|How to cite this article:|
Mubarak M, Abbas K. Antibody-mediated rejection: Importance of lactate dehydrogenase and neutrophilia in early diagnosis.Saudi J Kidney Dis Transpl 2011;22:1261-1262
|How to cite this URL:|
Mubarak M, Abbas K. Antibody-mediated rejection: Importance of lactate dehydrogenase and neutrophilia in early diagnosis. Saudi J Kidney Dis Transpl [serial online] 2011 [cited 2022 Oct 5 ];22:1261-1262
Available from: https://www.sjkdt.org/text.asp?2011/22/6/1261/87251
To the Editor,
We have read with great interest the article by Khan et al published in your valuable journal.  It is an interesting report linking elevated lactate dehydrogenase (LDH) levels and neutronphilia (NT) with early diagnosis of acute antibody-mediated rejection (AMR). It is an important contribution to the growing literature on this subject in the solid organ allografts from around the world.  Although we have not yet analyzed our whole data, but our experience shows that AMR is quite rare in our patients for obvious reasons. We have earlier reviewed 1210 dysfunctional renal allograft biopsies in 700 transplant recipients, and found only three cases of C4d-positive AMR.  We use all three recommended modalities for the diagnosis of AMR, i.e. graft biopsies, C4d and donor-specific antibodies (DSA), and it is highly unlikely that we are missing AMR. The extremely low AMR prevalence in our transplant population is understandable given the live related donor program, zero to very low panel reactive antibodies (PRA) and the very low rate of re-grafts in our set up. Although the authors of the subject study have not given the frequency or incidence data on AMR in their allograft biopsies, we assume that AMR is also rare in their practice. The finding of the usefulness of two simple and low-cost laboratory tests in the early diagnosis and monitoring of AMR by the authors of the subject study is an exciting discovery, but this finding, as the authors also suggest, has to be corroborated in larger studies. These tests are widely available, even in the most primitive laboratories in the third world countries. If their diagnostic usefulness is confirmed in further studies, the tests will certainly be considered as a significant contribution to the practice of transplant pathology in developing countries. In this context, it is imperative that we develop indigenous, low-cost tests for this purpose, or work in cooperation with transplant centers where sophisticated tests are available for precise diagnosis of cause of graft dysfunction.  The studies of this sort will definitely contribute new dimensions to the growing recognition of AMR.  But, a note of caution is in order. One needs to be very scrupulous, diligent and consistent in presenting the findings on such provocative topics. We would like to point out a few minor anomalies in the case report that need to be redressed.
The most important point is the lack of a precise time frame of various important events/interventions performed in the two cases, especially the timing of graft biopsies and C4d immunostaining, to justify the claim that unnecessary delay occurred in the first case. At our center, we have a highly pro-active renal allograft biopsy protocol. Renal allograft biopsies are done as soon as there is an unexplained rise (>20% above the baseline value) in serum creatinine levels. These are reported on the same day with urgent processing. C4d staining is also reported on the same day, as we use the immunoflourescence method, which is slightly rapid as compared with the immuno-peroxidase method used in the authors' laboratory and shown in [Figure 4].  Therefore, a delay on this account can easily be circumvented, especially in a live related transplant program. Moreover, as stated by the authors, elevated LDH levels are reflective of tissue necrosis or infarction, which is a late, rather than early event in AMR, it being the end result of preceding antibody attack on the allograft tissue. At least on theoretical grounds, it is contradictory to the claim of the authors that it is an early diagnostic marker.The neutrophilia (NT) observed by the authors as one of the parameters for the early diagnosis of AMR actually refers to elevated total leukocyte count (TLC) and not the neutrophil count, either relative or absolute. Moreover, there are some discrepancies in the use of units for these parameters, especially TLC count at different places. It is given as ×10 8 at many places or not given at all, as on page 527, column one, and line three. The units of LDH are also given incorrectly in [Figure 1], as u/L and not as IU/L.The legend of [Figure 3] states that fibrin thrombus is seen in the afferent arteriole at the glomerular hilum. It is, however, worth mentioning here that it is not possible to identify the afferent or efferent nature of the arterioles on morphology. A similar statement in the description of biopsy findings in case 1 also needs correction.The legend of [Figure 5] states that all three laboratory parameters are depicted, which is not true, as TLC count is not given.In the second case, it is stated that immunoadsorption was started soon after suspicion of AMR by the above laboratory tests, but the name of the adsorbing agent and duration of immunoadsorption is not given. We are also curious as to whether this procedure contributed to the better outcome in the second case.
We hope the clarification of the above points will help in better understanding the increasingly recognized problem of AMR as a significant cause of graft dysfunction throughout the world.
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