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II. ДИАГНОСТИКА
PERCUTANEOUS NEEDLE CORE BIOPSY AT DIAGNOSTICS OF RENAL ALLOGRAFT DYSFUNCTION: OUR EXPERIENCE IN APPLICATION OF BANFF-CLASSIFICATION
Enin E., Pismareva A.
National Scientific Center of Surgery named after A.N. Syzganov, Almaty, Kazakhstan Pathologicoanatomic laboratory
Abstract
In the given publication the results of researches showing a share and character of morphological changes in kidneys with application of Banff-classification at lifetime morphological diagnostics of renal allograft rejection are reflected. Research is carried out by studying bioptates in 31 cases at allograft rejection at related transplantation of a kidney.
UDC 616.61-089.843-076037
ABOUT THE AUTHORS: Evgeny A. Enin - head ofthe pathology laboratory, a high level certificate physician, e-mail: [email protected] Anastasiya V. Pismareva - pathologist, e-mail: [email protected]
Keywords
renal allograft biopsy, related transplantations, renal allograft rejection, lifetime morphological research.
Буйрект трансплантаттау дифункциясын диагностикалау кезшдеп TepiacTbi жщшке ине аркылы биопсия жасау: Banff-xiKTeyiH колданудагы тэж1рибем1з
Енин Е., Писмарева А.
А.Н. Сыз?ановатында?ы¥лттык,?ылымихирургия орталь™, Алматы, Казахстан Патологоанатомиялык,лабораториясы
Ацдатпа
Бул мацапада трансплантатты цабылдамаудыц курт аск,ынудыц OMip бойы морфологиялыц 03repicrepfliq белШ корсет жэне сипатын Banff-xiiaeyiH цолдануымен буйреш зерттеудщ нэтижелер1 корсетшедк Атапмыш зерттеу буйрект1 донордын, туыс^анынан ауыстырып цондыру кезшдеп кдбылдамаудыц курт аск,ынудыц 3! оциеада биоптаттарды зерделеу арцылы журпзшген.
АВТОРЛАР ТУРАЛЫ: Енин Евгений Альбертович
- А.Н. Сызтанов атын. YfXO-ныц патлотанатмиялык; зертханасыньщ Meqrepyiuici, жотарты санаттыдвр/гер, e-mail: [email protected] Письмарева Анастасия Владимировна - flepirep-патологанатом, e-mail: [email protected]
Туйш сездер
буйрек трансплантыньщ биоп-сиясы, туыстык трансплантаттау, буйрек трансплантатынын кабылдамаудьщ курт асцынуы, euip бойы морфологияльщдиа-гностикасы.
Чрескожная тонкоигольная биопсия при диагностике дисфункции почечного трансплантата: наш опыт применения Banff-классификации
Енин Е., Писмарева А.
Национальный научный центрхирургии им. А.Н. Сызганова, Алматы, Казахстан Патологоанатомическая лаборатория
Аннотация
В данной публикации отражены результаты исследований, демонстрирующие долю и характер морфологических изменений в почках с применением Banff-классификации при прижизненной морфологической диагностике кризов отторжения трансплантата. Исследование проведено путем изучения биоптатов в 31 случае кризов отторжения при родственной трансплантации почки.
ОБ АВТОРАХ:
Енин Евгений Альбертович -заведующий патолотоанатомиче-ской лабораторией, врач высшей катетории, e-mail: [email protected] Письмарева Анастасия Владимировна - врач-патолотоанатом, e-mail: anastasiyapismareva@ mail.ru
Ключевые слова
биопсия почечното трансплантата, родственная трансплантация, кризы отторжения почечното трансплантата, прижизненная морфологическая диатностика.
PERCUTANEOUS NEEDLE COREBIOPSYATDIAGNOSTICS OFRENALALLOGRAFTDYSFUNCTION: OUR EXPERIENCE IN APPLICATION OF BANFF-CLASSIFICATION
Fig. 1.
A. The glomerulus is presented by the afferent and efferent arterioles forming «Malpigie's" body.
Capsule'swalls are thin. In canaliculi nephrothelium is high cylindrical, in cytoplasm are visible small vacuole (H&E stain). B. Low magnification of cortexwith portions of two glomeruli, tubules, and interstitium and interlobular arterywith arteriolar branch (periodic acid-Schiff(PAS) stain).
C. Normal glomerulus with surrounding normal tubules and interstitium (Jones silver stain).
Fig. 2.
A. Humoral rejection, type II. Neutrophils are in peritubular capillaries and glomeruli; interstitial hemorrhage is present. Anti-donor class II antibodieswere demonstrable (H&E stain). B. Hyperacute rejection.
The cortex shows diffuse hemorrhage and neutrophils in peritubular capillaries with prominent glomerularthrombi 1 day aftertransplantation (H&E stain). C. Hyperacute rejection due to ABO incompatibility. (Immunofluorescence stain shows immunoglobulin M (IgM) in arterial walls).
Kidney transplant is the most common type of organ transplant and one of the most effective treatments for patients with end-stage renal disease. Management of patients with kidney transplant is a difficult clinical challenge and is often associated with a number of problems. Renal biopsy remains the gold standard by which essential diagnostic and prognostic information is obtained after kidney transplantation [8]. Biopsy methodologies have been devised to assess the acceptability of an organ before transplantation and to assess and predict renal allograft performance after implantation [11,16].
Standardization of renal allograft biopsy interpretation and reporting is necessary to guide therapy in transplant patients and to establish an objective end point for clinical trials of new anti-rejection agents [3]. The Banff Working Classification of Renal Allograft Pathology is an international schema recently developed to fill this need. The classification, which originated in a meeting held in Banff, Canada on August 2 to 4, 1991, was published in 1993, has been clinically validated in numerous studies, and is now widely used by center pathologists and in large international trials of immunosuppressive agents. Subsequent meetings have been held in Banff every two years to refine the classification. For National Institutes of Health clinical trials, a modification of the Banff grading system, the Collaborative Clinical Trials in Transplantation classification was developed; this classification and a clinical validation study were published in late 1997 [6,17].
Aim of research is practical application of the given classification of a pathology closely related
kidneys allotransplantation and revealing the value of a complex of morphological researches in dynamics.
The Banff classification characterizes five categories of renal allograft pathology: antibody-mediated rejection; suspicious of acute rejection; acute rejection; chronic sclerosing allograft nephropathy; and other-changes not considered due to rejection [9].
Was performed retrospective research biop-tates of kidney allograft for the period January of 2009 - February of 2015 years.
It was about 48 cases. 64,58 % (n-31) cases is related transplantations of a kidney. According to Banff-classification they have been divided into groups to investigated signs. Diagnostic categories of Banff 97 kidney allograft biopsies was following: the norm - 51,61% (n-16) (fig.1), antibody associated rejection - 3,22% (n-1), boundary changes - 9,67% (n-3), acute rejection - 9,67% (n-3), chronic nephropathy of transplantation -25,80% (n-8), with inherent morphological signs.
The antibody-associated rejection, presumably mediated by antibodies is typically characterized by the accumulation of polymorphonuclear leukocytes in glomerular and peritubular capillaries in the early period after transplantation, followed by damage to the endothelium and capillary thrombosis (fig.2). However, the histological diagnosis of acute ABMR is still problematic, especially in cases with few outward symptoms [7,14]. The studies using immunofluorescence to detect immunoglobulins (IgG, IgM and IgA), complement factors (C3, C4 and C1q) and fibrin are not very accurate [15].
PERCUTANEOUS NEEDLE CORE BIOPSYATDIAGNOSTICS OF RENAL ALLOGRAFTDYSFUNCTION: OUR
EXPERIENCEIN APPLICATION OFBANFF-CLASSIFICATION
Boundary changes - «suspicion'» on acute rejection [4]. This category is used when there is no intimai arteritis, but the presence of foci of weak tubulitis (fig.3).
In grafts undergoing acute rejection, T lymphocytes infiltrate and proliferate within the interstitial space, whence they invade renal tubules, causing tubulitis. Invading CD8 T lymphocytes, which have immunologic specificity for the allograft, cross the basement membrane of the tubule, where they proliferate and induce apop-tosis of tubular cells [1]. Sublethally injured tubular cells can also transform from their native epithelial phenotype into primitive mesenchymal myofibroblasts, promoting interstitial fibrosis [2,10]. Necrosis of tubular epithelial cells and basement membrane rupture cause urinary leakage, graft dysfunction, and progressive tubular atrophy [5,13]. The histologic characteristics of
vascular rejection (also termed arteritis or endarteritis) include the infiltration of vessels by mononuclear cells, endothelial-cell apoptosis, and the synthesis of matrix proteins and collagens by intimai myofibroblasts (fig.4).
Chronic allograft rejection - ongoing immune injury to the graft - is due to a failure to maintain sufficient immunosuppression to control residual antigraft lymphocytes or antibodies [2]. Its features include a progressive decline in renal function, invasion of the renal parenchyma by T cells, and persistent infiltration of the interstitium by T cells and macrophages [12]. Occasionally, one also sees smooth-muscle proliferation and hyperplasia in vessels, forming a neointima; focal destruction of internal elastic lamina; and finally, vascular occlusion (fig.5).
Finally, future advances in analysis of renal allograft biopsies can already be predicted, and the classification and grading of acute/active rejection will continue to evolve. The significance of specific morphologic findings-including glomerulus, arterioles, and infiltrates with unusual cellular features-for acute and chronic allograft function and outcome will continue to be investigated. Emphasis in biopsy assessment will shift from diagnosis to prediction of later allograft function and outcome, potentially enabling early intervention. Results of research have shown that lifetime morphological research of kidney transplant biopsies allows to give full representation about dynamics of a current, a stage of pathological process, a qualitative and quantitative estimation.
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Fig.5.
Fig. 3.
There is an edema in a glomerulus, full-blooded vessels. Canaliculi lumens are stretched, are marked bymononuclearcells: 1-3 in cross-section (weak tubulitis) (H&E stain).
Fig. 4.
A. Acute cellular rejection (type I). A diffuse mononuclear infiltrate
is present with edema and tubulitis (periodic acid-Schiff (PAS) stain).
B. Acute allograft glomerulopathy. This pattern of glomerular injury can occur as a feature of cellular or humoral rejection (PAS stain). C. Therewas no graft function. Tubules show severe acute damage, with a heavy infiltrate of neutrophils in intertubular capillaries (H&E stain).
Fig. 5.
A. Chronic allograft glomerulopathy. Mesangial hypercellularity and duplication ofthe glomerular basement membrane are prominent (PAS stain). B. Chronic allograft arteriopathy. Expansion of the intima with foam cells and scattered infiltrating mononuclear cells are shown in a nephrectomy 2 years aftertransplantation (elastin stain). C. Sclerosis of previous glomeruli, abundance of fibrous connective tissue. Expressed lymphoid reaction without tubulitis. Compression of canaliculi and reduction in number with expressed atrophy (H&E stain)
PERCUTANEOUS NEEDLE CORE BIOPSY AT DIAGNOSTICS OF RENAL ALLOGRAFT DYSFUNCTION: OUR EXPERIENCED APPLICATION OFBANFF-CLASSIFICATION
References
1. Bestard 0, Nickel P, Cruzado JM, et al. Circulating alloreactive T cells correlate with graft function in longstanding renal transplant recipients. J Am Soc Nephrol 2008;19:1419-29.
2. BonsibSM,Abul-EzzSR,Ahmadl,etal. Acute rejection-associated tubular basement membrane defects and chronic allograft nephropathy. Kidney Int 2000;58:2206-14.
3. Cornell LD, Smith RN, Colvin RB. Kidney transplantation: mechanisms of rejection and acceptance. Annu Rev Pathol. 2008; 3:189220.
4. De Freitas DG, Sellare ?s J, Mengel M et al. The nature of biopsies with 'borderline rejection' and prospects for eliminating this category. Am J Transplant 2012; 12: 191-201.
5. Elshafie M, Furness PN. Identification of lesions indicating rejection in kidney transplant biopsies: tubulitis is severely under-detected by conventional microscopy. Nephrol Dial Transplant 2012; 27: 1252-1255.
6. Furness PN, Taub N, Assmann KJ et al. International variation in histologic grading is large, and persistent feedback does not improve reproducibility. Am J Surg Pathol 2003; 27: 805810.
7. Halloran PF. Immunosuppressive drugs for kidney transplantation. N Engl J Med 2004; 351:2715-29.
8. Hoffmann SC, Hale DA, Kleiner DE, et al. Functionally significant renal allograft rejection is defined by transcriptional criteria. Am J Transplant 2005; 5: 573-81.
9. Howie AJ. Problems with BANFF. Transplantation. 2002; 73(9):1383-4, a comment on Mc-
Carthy GP, Roberts IS. Diagnosis of acute renal allograft rejection: evaluation of the Banff 97 Guidelines for Slide Preparation. Transplantation 2002; 73: 1518-1521
10. Kalluri R. EMT: when epithelial cells decide to become mesenchymal-like cells. J Clin Invest 2009; 119:1417-9.
11. Li XC, Rothstein DM, Sayegh MH. Costimula-tory pathways in transplantation: challenges and new developments. Immunol Rev 2009; 229:271-93.
12. Nankivell BJ, Borrows RJ, Fung CL.O'Connell PJ, Allen RD, Chapman JR. The natural history of chronic allograft nephropathy. N Engl J Med 2003; 349:2326-33.
13. Robertson H., Kirby JA. Post-transplant renal tubulitis: the recruitment, differentiation and persistence of intra-epithelial T cells. Am J Transplant 2003;3: 3-10.
14. Sis B, Mengel M, Haas M, Colvin RB, Halloran PF, Racusen LC, et al. Banff '09 Meeting Report: antibody mediated graft deterioration and implementation of Banff working groups. Am J Transplant 2010; 10:464-71.[Pubmed]
15. Stegall MD, Gloor JM. Deciphering antibody-mediated rejection: new insights into mechanisms and treatment. Curr Opin Organ Transplant 2010;15:8-10.
16. Stratta R J, Sundberg AK, Rohr MS, et al. Optimal use of older donors and recipients in kidney transplantation. Surgery 2006; 139:324-33.
17. Terasaki PI. Antibody response to homograft. I. Preliminary studies of the time of appearance of lymphoagglutinins upon homografting. Am Surg 1959; 11:896-9.[Pubmed]
