Reproducibility of the Banff classification in subclinical kidney transplant rejection

The Banff classification for kidney allograft pathology has proved to be reproducible, but its inter and intraobserver agreement can vary substantially among centres. The aim of this study was to evaluate Banff reproducibility of surveillance renal allograft biopsies among renal pathologists from different transplant centres. This study included 32 renal transplant patients with stable graft function. Biopsies were performed 2 and 12 months post-transplant. Histology was interpreted according to the Banff schema by three renal pathologists, and inter and intraobserver agreement were measured. The best reproducibility was obtained for the presence or absence of acute rejection (AR), with kappa values ranging from moderate (kappa = 0.47; p = 0.006) to good (kappa = 0.72; p = 0.0001). However, the agreement for 'suspicious for AR' category was poor between all observers. For scoring and grading interstitial inflammation and intimal arteritis the agreement were poor and moderate, respectively. Reproducibility for the presence or absence of chronic allograft nephropathy (CAN) was heterogeneous, ranging from poor (kappa = 0.13; p = NS) to moderate (kappa = 0.56; p = 0.007). Scoring chronic changes such as fibrous intimal thickening gave a reasonable interobserver agreement. Intraobserver reproducibility was good for presence or absence of AR, but was poor for the diagnosis of CAN. In conclusion, histologic analysis of stable renal allografts based on Banff criteria showed a good agreement for the diagnosis of AR and a reasonable kappa for CAN, but reproducibility for scoring and grading showed a substantial interobserver variation.     

A new alloantigen-independent control for chronic allograft nephropathy rat models

BACKGROUND: Isografts are used as controls in many transplant experiments. Our laboratory and others have noticed histological changes in control isograft groups of rats similar to allograft groups, suggesting alloantigen-independent factors contributing to chronic allograft nephropathy. However, the isograft model as a nonalloantigen control is flawed because of the potential of unrecognized minor antigen differences between rats. We designed a study using autografts to isolate alloantigen-independent factors in the rat renal transplant allograft model. MATERIALS AND METHODS: Male Lewis rats weighing 150-250 g underwent a procedure designed to mimic the injury of renal transplant, in which the left kidney was perfused with cold University of Wisconsin solution and subjected to similar cold and warm ischemic times as Lewis isograft rats undergoing renal transplanation. RESULTS: Six autograft rats were compared to five isograft and three single nephrectomy rats. Autograft rats showed normal kidney function according to serum BUN, Cr, and urinary protein. At 360 days, four of six autografts displayed normal renal parenchymal histology, whereas the remaining two autografts displayed histological changes scored as Banff acute rejection 1a and 1b. At sacrifice time, four of five isografts showed histological changes scored as Banff chronic rejection 1 and the single nephrectomy group showed normal histology in the remaining native kidney. CONCLUSIONS: Our data demonstrate that the chronic nephropathy observed in the isograft cannot be completely freed from suspicion of immunological origin. We propose that the autograft model for rat renal transplant research is a better nonimmunologic control than the isograft model for chronic allograft nephropathy.     

The role of C4d immunostaining in the evaluation of the causes of renal allograft dysfunction.

BACKGROUND: Renal biopsy is the gold standard for diagnosis of acute rejection in renal transplant recipients. The Banff (1997) classification was revised in 2003 incorporating morphological criteria and C4d immunostaining for the diagnosis of acute antibody-mediated rejection. AIMS: The aim of this study was to evaluate the role of histomorphology and C4d immunostaining in indicated renal allograft biopsies with a clinical follow-up for a minimum duration of 1 year. MATERIAL AND METHODS: Histological analysis and C4d immunostaining were performed on 132 needle core biopsies and 2 nephrectomy specimens from 107 patients from July 2004 to June 2005. RESULTS: Histological analysis revealed 59 cases of acute rejection, 10 biopsies of acute tubular necrosis, 41 cases of chronic allograft nephropathy (CAN), either alone or in combination with other diseases, and 18 biopsies of normal morphology. There were four cases of BK nephropathy (BK N) and eight cases had miscellaneous diagnoses. C4d immunostaining was performed on 126 biopsies. Overall, the prevalence of C4d positivity was 45% (57 of 126). Fifty-five percent (28 of 51) of the cases of acute rejection showed C4d positivity including 81% of presumptive antibody-mediated rejection (P-AbAR), 20% acute cellular rejection and 58% acute cellular rejection + P-AbAR. Overall C4d positivity was 37% in chronic allograft nephropathy. Acute tubular necrosis and borderline rejection showed 25 and 50% C4d positivity, respectively. Amongst various histological features, capillary margination of polymorphs and dilatation of peritubular capillaries (PTC-D) showed significant association with C4d positivity (P < 0.005). In cases of CAN, transplant glomerulopathy had significant association with C4d positivity. C4d-positive cases had a higher mean value of serum creatinine at the time of biopsies. CONCLUSION: It is concluded that C4d staining is a useful adjunct marker of the humoral limb of rejection, both in early and late post-transplant periods.     

Effect of histological damage on long-term kidney transplant outcome

BACKGROUND: Chronic renal allograft failure remains a major challenge to overcome. Factors such as donor quality, delayed graft function (DGF), acute rejection, and immunosuppression are known to affect long-term outcome, but their relationship to histological damage to graft outcome is unclear. METHODS: Protocol kidney biopsies (n=112) obtained at 3 months after transplantation yielded 102 with adequate tissue. Histology was scored by the Banff schema, and compared with implantation biopsies (n=91), repeat 12-month histology (n=39), decline in serum creatinine and serial isotopic glomerular filtration rate, onset of chronic allograft nephropathy (CAN), and actuarial graft survival censored for death with a functioning graft. RESULTS: At a median follow-up of 9.3 years, 20 patients had graft failure and 26 died with a functioning graft. Banff chronic nephropathy was present in 24% of 3-month biopsies, and was predicted by microvascular disease in the donor, cold ischemia, DGF, and acute vascular rejection (P<0.001). Acute glomerulitis at 3 months correlated with segmental glomerulosclerosis at 12 months, subsequent recurrent glomerulonephritis, and graft failure (P<0.01). Subclinical rejection at 3 months occurred in 29% of biopsies, correlated with prior acute rejection and HLA mismatch, and led to chronic histological damage by 12 months (r=0.25-0.67, P<0.05-0.001). Subclinical rejection, arteriolar hyalinosis, and tubulitis present at 3 months had resolved by 12 months. The 10-year survival rates for Banff chronic nephropathy were 90.4% for grade 0, 81.0% grade 1, and 57.9% for grades 2 or greater (P<0.01). Early tubulointerstitial damage at 3 months profoundly influenced graft survival beyond 10 years. CAN was predicted by kidney ischemia, 3-month chronic intimal vascular thickening, tubular injury, proteinuria, and late rejection. Chronic fibrointimal thickening of the small arteries and chronic interstitial fibrosis at 3 months independently predicted graft loss and decline in renal function (P<0.05-0.001). CONCLUSIONS: Early transplant damage occurs in the tubulointerstitial compartment from preexisting donor kidney injury and discrete events such as vascular rejection and DGF. Subsequent chronic damage and graft failure reflect accumulated previous injury and chronic interstitial fibrosis, vascular impairment, subclinical rejection, and injury from late rejection. CAN may be conceptualized as the sequelae of incremental and cumulative damage to the transplanted kidney. The duration of graft survival is dependent and predicted by the quality of the transplanted donor kidney combined with the intensity, frequency, and irreversibility of these damaging insults.     

Poly(ADP-ribose) polymerase expression in kidney transplantation: from alfa (alpha) to Omega (Omega)

INTRODUCTION: Overactivation of the enzyme poly(ADP-ribose) polymerase (PARP-1) can be induced by ischemia-reperfusion and involved in the renal injury subsequent to kidney transplant. The poly(ADP-ribosy)lation mechanism alters free radical-induced DNA damage, which is repair by PARP-1 polymer. However, PARP-1 overexpression induces cellular necrosis. Our aim was to study the immunohistochemical PARP-1 expression in kidney transplant biopsies associated with various events. MATERIALS AND METHODS: We studied the nuclear expression of PARP-1 in kidney tubule cells by immunohistochemistry using the monoclonal antibody PAR01 in donor biopsies without acute tubular necrosis (ATN) (n = 60; controls), allografts that suffer ATN (n = 90) or an episode of acute humoral rejection (n = 12) or acute tubulointerstitial rejection (n = 25), or chronic allograft nephropathy (n = 25). Furthermore, we also studied protocol biopsies with subclinical rejection (n = 60). Renal lesions in transplant biopsies were graded blindly using 1997 Banff criteria without any clinical information. RESULTS: Biopsies without morphological features of ATN, namely acute tubulointerstitial rejection, borderline or subclinical rejection, showed lesser PARP-1 expression compared with biopsies with ATN or with ischemic mechanism of acute humoral rejection or chronic allograft nephropathys. We observed an inverse relation between PARP-1 expression and renal function (P < .001). Overall, renal biopsies showing ATN revealed greater expression of PARP-1 (r = 0.785, Pearson test). A significant relationship with PARP-1 expression was demonstrated with renal function (effective diuresis, serum creatinine levels) and pretransplant cold ischemia time (P < .001). CONCLUSION: Kidney transplant events including ischemia were associated with the highest PARP-1 expression and worse allograft renal function.     

Acute rejection-associated tubular basement membrane defects and chronic allograft nephropathy

BACKGROUND: Acute rejection is a major risk factor for chronic allograft nephropathy, although the link(s) between these events is not understood. The hypothesis of this study is that alterations in tubular basement membranes (TBMs) that occur during acute rejection may be irreversible and thereby play a role in the development of chronic allograft nephropathy. METHODS: Fourteen renal transplant patients were selected, each having had two or more biopsies performed (42 total). All biopsies were scored for acute and chronic rejection using Banff 1997 criteria. The initial biopsy showed only acute interstitial rejection (type I rejection). No biopsies contained significant chronic arterial lesions of chronic vascular rejection. The entire cortex was examined on Jones methenamine silver-stained sections at x400 for interruption in TBM staining. The number of tubules with TBM abnormalities was counted, and the renal cortical area was measured by image analysis. Periodic acid-Schiff/immunoperoxidase stain was performed on 12 acute rejection biopsies stained for laminin, cytokeratin 7, CD3, CD20, and CD68. Controls consisted of 11 biopsies (8 negative for rejection and 3 acute tubular necrosis). RESULTS: Numerous TBM alterations in silver staining were identified as being associated with acute rejection and tubulitis, consisting of abrupt TBM discontinuities and/or extreme attenuation with segmental or complete absence of TBM. A loss of TBM matrix proteins was confirmed by absent laminin staining in areas of acute rejection and tubulitis. There was herniation of tubular cells into the interstitium through TBM defects confirmed by cytokeratin staining. The TBM defects were spatially associated with inflammatory cells, particularly macrophages. When the biopsies were divided into two groups, <10 and> 10 TBM breaks/mm2, there were statistically significant morphologic and clinical correlations. The number of TBM disruptions correlated with the serum creatinine at the time of biopsy, a combined Banff t + i score, the difference in tubular atrophy between the initial and most recent biopsy and the difference between the nadir creatinine and most recent creatinine. CONCLUSION: Damage to TBM develops in acute rejection as a consequence of interstitial inflammation and tubulitis. These lytic events correlate with the later development of clinical and morphologic evidence of chronic injury in the absence of arterial injury of chronic rejection. We suggest that chronic allograft nephropathy may have an inflammatory interstitial origin.     

SDF-1 expression is elevated in chronic human renal allograft rejection

The exact mechanism of acute and chronic allograft rejection still remains unclear. The chemokine SDF-1 as mediator of allograft rejection has been under intensive investigation in liver, cardiac and bone marrow transplantation, whereas in renal transplantation, there are no reports about SDF-1 to date. This study was performed to evaluate if SDF-1 might also play an important role in human renal graft biopsies. One hundred and ninety formalin-fixed, paraffin-embedded renal allograft biopsies were included in the analysis from patients with normal renal graft morphology (according to Banff 97 classification grade 1, n = 84), with acute interstitial rejection (Banff grade 4 type I, n = 10), with acute vascular rejection (Banff grade 4 type II, n = 21), with chronic allograft nephropathy (CAN, Banff grade 5, n = 23), and without rejection but with various other lesions (Banff grade 6, n = 42). SDF-1 was localized by immunohistochemistry. In biopsies with CAN, SDF-1 expression was significantly elevated in interstitial infiltrates and infiltrating neointimal cells of arteries compared with biopsies with normal renal graft morphology. This is the first study describing a role of SDF-1 in human renal allograft rejection. We were able to demonstrate in a large number of biopsies an upregulation of SDF-1 in patients with CAN. Whether SDF-1 has pro-inflammatory or protective properties in this setting has to be evaluated in further trials.     

One-year routine renal transplant biopsies in children

In our institution, systematic renal graft biopsies are performed 1 year after transplantation before deciding to switch to alternate-day steroid therapy, which has been shown to be beneficial for statural growth. We analyzed the results of systematic graft biopsies in 145 children with a creatinine clearance > or =45 ml/min per 1.73 m2. Biopsies were classified according to Banff diagnostic categories. Normal parenchyma was observed in 19 cases (13%), non-specific lesions in 42 cases (29%), chronic allograft nephropathy grade 1-3 in 68 cases (49%), and acute rejection in 8 cases (5%). Clinicopathological correlations indicated that patients with chronic allograft nephropathy had received kidneys from older donors, with longer cold ischemia time and with a higher incidence of delayed graft function. There was a strong correlation between the donor age and the presence of vascular lesions. There was also a good correlation between the severity of histological lesions and the occurrence of acute rejection episodes during the 1st year after transplantation. Renal function remained stable for up to 10 years in patients with normal parenchyma or non-specific lesions, while serum creatinine levels increased after the 2nd year in patients with chronic allograft nephropathy.     

Expression of the chemokine receptor CXCR3 in human renal allografts--a prospective study.

BACKGROUND: Mechanisms involved in the recruitment and activation of inflammatory cells during renal allograft injury are still incompletely understood. Since chemokines play pivotal roles in this process, our prospective study was performed to evaluate further the role of the chemokine receptor CXCR3. METHODS: A total of 138 biopsies were included from patients without rejection and unaltered morphology (according to Banff 97 classification grade 1, n = 49), with acute interstitial rejection (Banff grade 4 type I, n = 8), with acute vascular rejection (Banff grade 4 type II, n = 23), with chronic allograft nephropathy (Banff grade 5, n = 16), without rejection but with various other lesions (Banff grade 6, n = 36) and from pre-transplant kidneys (n = 6). The expression of CXCR3-, CD4- and CD8-positive cells was localized by immunohistochemistry and quantified by image analysis. RESULTS: CXCR3 was expressed by infiltrating inflammatory cells, but not by intrinsic renal structures. CXCR3-positive cells were found to be involved in tubulitis and vascular rejection. The area of CXCR3-positive staining was significantly larger in biopsies with acute interstitial rejection (P<0.001) and acute vascular rejection (P<0.001) as compared with normal renal graft biopsies. There was a strong morphological and numerical correlation between CXCR3 and both CD4- and CD8-positive T cells, respectively. CONCLUSIONS: A significant part of both CD4- and CD8-positive T cells express the chemokine receptor CXCR3. During renal allograft rejection, the number of these cells increases significantly at the site of injury and might be targeted by CXCR3 blocking agents.     

Prevalence and immunohistochemical findings of subclinical kidney allograft rejection and its association with graft outcome

Subclinical acute rejection (SAR) occurs in about 30% of stable renal transplant patients and may be a risk factor for a poor allograft outcome. In the present study, the prevalence and clinical features of subclinical rejection, and the expression of immune activation markers in surveillance graft biopsies were assessed and correlated with late graft outcomes. Protocol biopsies were obtained at 2 and 12 months post-transplant in 32 and 26 patients, respectively, with stable renal function. The Banff 1997 criteria were used for histological diagnosis. Graft function and survival and proteinuria were assessed during the 36 months of follow-up. Immunohistochemical evaluation of cell subpopulations and immunoactivation markers were performed on protocol biopsies. The prevalence of SAR at 2 months and of chronic allograft nephropathy (CAN) at 12 months in representative biopsies was 55 and 50%, respectively. Patients with SAR presented mononuclear cell infiltration with an increased expression of CD3, CD4, CD68, IL-2R and granzyme B. Kidney graft function was significantly worse in patients with SAR at 2 months who had chronic rejection on biopsy at 12 months, but SAR was not associated with a worse graft function, greater proteinuria or a lower graft survival in 3 yr of follow-up. In conclusion, we found an elevated prevalence of SAR at 2 months after transplantation with an increased expression of activation markers. Although an association of SAR with poor graft outcome was not observed, our results suggest that SAR is an immunologically active process and underscore the importance of protocol biopsies in the surveillance of transplanted kidneys.     

International variation in the interpretation of renal transplant biopsies: report of the CERTPAP Project.

BACKGROUND: The Banff working formulation of renal transplant pathology is intended to have international application. There remains a need to develop methods to harmonize the application of such grading systems between laboratories. Banff grades do not always permit precise management decisions to be made. Alternative schemes have been devised for the diagnosis of acute rejection, but there have been no independent tests of the different approaches. METHODS: Sections from 55 renal transplant biopsies were circulated around the laboratories of 22 major transplant units for the Convergence of European Renal Transplant Pathology Assessment Procedures (CERTPAP) Project. Participating pathologists were asked to grade 32 different histological features, without any clinical information. After each circulation of five cases, feedback was provided to participants. Statistical evidence of improvement in interobserver variation was sought. At the end of the study, correlations with the original clinicopathological diagnosis were sought. RESULTS: Interobserver variation was greater than has previously been reported. For every feature studied, some pathologists consistently under-grade or over-grade. There was relatively little evidence of improvement in interobserver variation as a result of the feedback system. No single feature permitted a reliable diagnosis of acute rejection. Applying the Banff and CCTT schemas to the histological grades showed no clear diagnostic advantage for either system, but a simple computer-based inference network, which combined data from 12 histological features, out performed either approach. Within the "protocol" biopsies studied, long-term survival correlated better with "acute" than with "chronic" histological features. CONCLUSIONS: These results do not undermine the value of the Banff classification, but they demonstrate a need for caution when translating biopsy results between institutions. It is obvious that evaluation of biopsies in multicenter trials must be done in one center. In the management of individual patients, the need to interpret Banff grades in the light of local experience and clinical information is stressed.     

DNA fragmentation in acute and chronic rejection after renal transplantation

Acute and chronic rejections are important denominators for the long-term function of renal grafts. One important indicator of cell damage is enzymatic DNA fragmentation. To investigate possible mechanisms, the rate of DNA fragmentation (TUNEL staining), the expression of tissue transglutaminase II (a marker of advanced DNA damage), and 8-hydroxy-2'-deoxyguanosine (8-OhdG), an indicator of oxidative injury of nucleic acids, were studied by immunohistochemistry. Semithin sections of renal biopsies revealed 23 patients to show acute interstitial rejections (Banff 97 IA, IB); eight patients, acute vascular rejection (Banff 97 IIA, IIB); and 20 patients, chronic allograft nephropathy (Banff 97 I to III). Correlations were calculated between apoptotic cells and serum creatinine at the time of biopsy and after 6 months. In acute rejection, the proximal tubular cells were apoptotic, particularly in regions with mononuclear infiltrates. In consecutive sections, these apoptotic tubular cells also showed damage by reactive oxygen species (positive 8-OhdG staining). Patients with acute interstitial rejection revealed the highest number of tubular DNA fragmentation (14.9 +/- 10.3) versus chronic allograft nephropathy (9.2 +/- 5.6) as TUNEL-positive cells per 80,000 micro m(2) (P < .05). Patients with acute vascular rejection showed a low degree of tubular apoptosis (6.8 +/- 5.1). There was no significant difference in glomerular DNA fragmentation between acute interstitial and chronic rejections: acute interstitial rejection = 7.1 +/- 5.9 versus chronic allograft nephropathy=6.1 +/- 3.9 TUNEL-positive cells per 80,000 micro m(2). There was a significant negative correlation between the degree of tubular (P < .01) and glomerular (P < .05) apoptosis and the serum creatinine at the time of biopsy as well as after 6 months in all patients irrespective of the Banff class. However, there was heterogeneity in the correlation between renal function and the degree of apoptosis in the glomerular and tubular compartments in the various Banff classes. A positive correlation (P < .01) was observed between the degree of tubular apoptosis and serum creatinine at 6 months after biopsy among patients with acute vascular rejection (Banff 97 IIA, IIB). The present data revealed a high degree of tubular DNA fragmentation associated with oxidative stress in acute interstitial rejection. Nevertheless, apoptosis did not generally negatively influence future renal function and may be important to clear proliferating cells. Apoptosis may also play a different pathophysiological role depending on the type of rejection.     

Superiority of virtual microscopy versus light microscopy in transplantation pathology

Virtual microscopy has begun to change conventional pathology practice. We tested the reliability of this new technology in transplantation pathology. We studied 40 kidney transplant biopsies for cause and compared reproducibility of Banff scores using virtual slides versus glass slides. Three glass slides per biopsy were scanned as high-resolution digital slides using Aperio ScanScope. Three pathologists independently reviewed the biopsies: twice by glass slides and twice by virtual slides. Eleven histopathological lesions were scored and used to construct diagnosis according to Banff criteria. The intra-observer reproducibility of Banff scores was substantially good using either virtual slides or glass slides (mean κ: 0.69 vs. 0.64, p>0.05). The inter-observer reproducibility of Banff scores was better in virtual slides than in glass slides (mean κ: 0.42 vs. 0.28, p<0.001). Among the lesions, transplant glomerulopathy scoring by virtual slides showed the highest inter-observer reproducibility, with a similar accuracy to glass slides. The agreement for acute rejection between virtual and glass slides was not different from the agreement between two readings of glass slides. Thus, virtual microscopy is a reliable and more reproducible technology and has several advantages over glass slides, e.g., accessibility via internet, no fading. We recommend virtual microscopy for transplant diagnostics, including utilization for clinical trials.     

Protocol biopsies after kidney transplantation

Numerous studies have investigated features of allograft injury in renal biopsies obtained in stable kidney transplants. Evaluation of protocol biopsies has revealed a considerably high prevalence of subclinical acute rejection (SAR) and chronic allograft nephropathy (CAN) already in early phases after transplantation. The meanwhile well-established association of SAR and CAN in protocol biopsy with long-term allograft failure and the finding of superior allograft outcome after treatment of SAR in a randomized prospective study may point to clinical relevance of this procedure. In this review, potential benefits and risks associated with kidney allograft biopsy in stable renal transplant recipients are discussed.     

Histopathological diagnosis of acute and chronic rejection in pediatric kidney transplantation

ABO-compatible as well as ABO-incompatible kidney transplantation are well established in the pediatric population. There are particularities in the histopathological evaluation of pediatric kidney transplant biopsies as for example the recurrence of certain diseases different from the adult population. Furthermore, the challenging transition of pediatric renal transplant recipients to adulthood is associated with an increased rate of non-adherence triggered rejection episodes. With modern immunosuppressive drugs, T-cell-mediated rejection of renal allografts is well controlled. In contrast, antibody-mediated rejection (AMR) is increasingly recognized as one of the major reasons for allograft loss. However, the 2001 diagnostic Banff criteria for antibody-mediated rejection require further refinement, as the morphological spectrum of AMR expands while effective therapeutic strategies are lacking. For example, endarteritis, which traditionally has been attributed to T-cell-mediated rejection, has recently been shown to be part of the AMR spectrum in some cases. Many findings in transplant renal biopsies are not specific for a certain disease but need consideration of differential diagnoses. To use the term “chronic allograft nephropathy” as a diagnostic entity is no longer appropriate. Therefore, the precise identification of specific diseases is paramount in the assessment of transplant renal biopsies in order to enable tailored therapeutic management.     

Glomerulonephritis is the major cause of proteinuria in renal transplant recipients: histopathologic findings of renal allografts with proteinuria

The proteinuria in renal allograft recipients has been regarded as a sign of poor prognosis. The causes of post-transplant proteinuria include chronic rejection, chronic transplant glomerulopathy, glomerulonephritis (GN), acute rejection, and cyclosporine nephrotoxicity. Among them, chronic rejection is known to be most frequent. We analyzed the histopathologic findings of renal allograft biopsies in 197 Korean recipients with proteinuria. Among them, 26 patients developed proteinuria over 500 mg/d. All patients received baseline immunosuppression with cyclosporine. From 26 patients with post-transplant proteinuria, 29 biopsies were performed and their histologic diagnoses were immunoglobulin A nephropathy (IgAN) in 17, IgAN combined with chronic allograft nephropathy in 1, focal segmental glomerulosclerosis in 2, crescentic GN in 1, membranous GN in 1, diabetic nephropathy in 1, acute tubulointerstitial nephritis in 1, and chronic rejection in 3 biopsies. The remaining two biopsies showed nonspecific findings. The most common cause of post-transplant proteinuria was IgAN (62% of biopsies). The incidence of chronic rejection was relatively low and predominant cyclosporine-associated changes were not observed. In conclusion, our data suggest that the main causes of post-transplant proteinuria in Korea are primary glomerulonephritides rather than chronic rejection or cyclosporine nephrotoxicity, and the kidney allograft biopsies from patients with proteinuria should be handled as native kidney.     

The macrophage is the predominant inflammatory cell in renal allograft intimal arteritis

BACKGROUND: Intimal arteritis defines acute vascular rejection in the Banff 97 schema. The arteritis is generally considered to be lymphocytic, although the cellular infiltrate in tubulitis is composed of both lymphocytes and macrophages. This study aimed to determine the extent of macrophage involvement in renal allograft intimal arteritis. METHODS: We obtained archival biopsy material from 57 biopsies of 34 renal allografts transplanted between March 1999 and February 2002. All biopsies were diagnostic. We examined clinical and histological parameters. Biopsies were graded using the Banff 97 criteria. We identified macrophages and memory T cells using immunohistochemistry for CD68 and CD45RO, respectively. RESULTS: In all, 24 biopsies showed borderline rejection, and 12 biopsies showed grade IA, 13 showed grade IB, and 8 showed grade II or III acute rejection. Both lymphocytes and macrophages were present in the tubulointerstitium in all grades of acute rejection. We identified intimal arteritis in 10 vessels in eight biopsies. The infiltrating cells invariably included CD68-positive cells; however, we saw intimal CD45RO-positive cells in only seven vessels. There were significantly more CD68-positive cells than CD45RO-positive cells (mean, 9.5 vs. 4.4 positive cells per vessel, P< 0.01). CD45RO cells were never the predominant component of the intimal inflammatory infiltrate. CONCLUSIONS: In the intimal arteritis of biopsies graded as Banff II or III acute rejection, the infiltrating cells were predominantly macrophages. T cells were in the minority. This finding challenges the assumption that the mononuclear cells in intimal arteritis are predominantly lymphocytic.     

移植肾活组织检查191例的病理学研究

目的：研究供肾可能携带的病变及移植肾在术后出现合并症时间相应的病理组织学变化。方法对191例移植肾进行了活组织检查（以下简称“活检”,其中术中活检52例,术后活检139例,并进行病理学诊断与分类。结果（1）52例术中活检,40例（76．92％）正常,余12例（23．07％）供肾携带病变,其中细小动脉硬化3例（5．77％）、间质炎症4例（7．69％）、局部肾小管轻度萎缩3例（5．77％）、肾小管上皮细胞变性2例（3．84％）。（2）139例术后活检中明确诊断的134例（96．40％）,其中正常19例（13．66％）,超急性排斥反应（SAR）1例（0．71％）疑为急性排斥反应／临界性变化（S／B）15例（10．795）,急性排斥反应（AR）23例（16．54％、慢性移植肾肾病（CNA）37例（26．61％）、环孢素肾毒性损伤（CsA-NT)29例（20．80％）、急性肾小管坏死（ATN）8例（5．75％）、复发性肾炎（RN）2例（1．43％）、难以明确诊断的5例（3．59％）。（3）免疫细胞化学色显示AR时,侵入肾小管上皮内的Leu-7阳性细胞数增加,间质内CD68阳性细胞数明显增加。结论活检是诊断术后多种合并症的有效手段;CAN可在术后3个月发生;侵入肾小管上皮的Leu－7阳性细胞是协助诊断AR的有效指标。