The importance of urinary thromboxane B2 excretion in the diagnosis of acute renal rejection

To establish whether or not urinary excretion TxB2 is a useful parameter in the diagnosis of acute renal rejection, 45 renal transplant patients were studied and classified in four groups: Group A. Ten observations of satisfactory clinical outcome (without either acute rejection or tubular necrosis). Urinary TxB2 was initially increased but had settled to normal by the 3rd postoperative day. Two patients had subsequent increases. Group B. Twenty-five episodes of acute rejection on a previously satisfactorily functioning graft. Nineteen had increases in TxB2 values before serum creatinine increased. Group C. Five episodes of tubular necrosis without acute rejection. The evolution was similar to Group A. Group D. Nine acute episodes of rejection on kidneys with tubular necrosis. The urinary output of TxB2 was increased from the beginning. This increase was maintained until the rejection was treated. This group had the highest values of urine TxB2. The principal significance of this parameter lies in its precocity and in its utility for diagnosis of acute rejection in the graft with tubular necrosis, as the persistence of raised values of TxB2 in the urine beyond the 3rd postoperative day is highly suggestive of an acute rejection.     

Non-invasive diagnosis of acute rejection in kidney transplants with delayed graft function

Delayed graft function (DGF) often occurs in kidney transplants from deceased donors. We wanted to provide studies giving more accurate non-invasive tests for acute rejection (AR). Using real-time PCR, we examined the expression of cytolytic molecules such as perforin, granzyme B, and fas-ligand along with serpin proteinase inhibitor-9. We also measured the expression of FOXP3, a characteristic gene of T-regulatory cells known to be involved in AR. These studies were conducted on peripheral blood monocytes, urinary cells, and 48 surveillance kidney biopsies taken from a total of 35 patients with DGF. Of these patients, 20 had a histopathological diagnosis of AR, whereas other 28 had characteristics of acute tubular necrosis (ATN). Expression of cytolytic and apoptotic-associated genes in the biopsy tissue, peripheral blood leukocytes, and urinary cells was significantly higher in patients with AR than that in patients with ATN. Diagnostic parameters associated with FOXP3 gene expression were most accurate in peripheral blood leukocytes and urine cells with sensitivity, specificity, positive and negative predictive values, and accuracy between 94 and 100%. Our study shows that quantification of selected genes in peripheral blood leukocytes and urinary cells from renal transplant patients with DGF may provide a useful and accurate non-invasive diagnosis of AR.     

Urinary Cell mRNA Profiles and Differential Diagnosis of Acute Kidney Graft Dysfunction

Noninvasive tests to differentiate the basis for acute dysfunction of the kidney allograft are preferable to invasive allograft biopsies. We measured absolute levels of 26 prespecified mRNAs in urine samples collected from kidney graft recipients at the time of for-cause biopsy for acute allograft dysfunction and investigated whether differential diagnosis of acute graft dysfunction is feasible using urinary cell mRNA profiles. We profiled 52 urine samples from 52 patients with biopsy specimens indicating acute rejection (26 acute T cell–mediated rejection and 26 acute antibody-mediated rejection) and 32 urine samples from 32 patients with acute tubular injury without acute rejection. A stepwise quadratic discriminant analysis of mRNA measures identified a linear combination of mRNAs for CD3ε, CD105, TLR4, CD14, complement factor B, and vimentin that distinguishes acute rejection from acute tubular injury; 10-fold cross-validation of the six-gene signature yielded an estimate of the area under the curve of 0.92 (95% confidence interval, 0.86 to 0.98). In a decision analysis, the six-gene signature yielded the highest net benefit across a range of reasonable threshold probabilities for biopsy. Next, among patients diagnosed with acute rejection, a similar statistical approach identified a linear combination of mRNAs for CD3ε, CD105, CD14, CD46, and 18S rRNA that distinguishes T cell–mediated rejection from antibody-mediated rejection, with a cross-validated estimate of the area under the curve of 0.81 (95% confidence interval, 0.68 to 0.93). Incorporation of these urinary cell mRNA signatures in clinical decisions may reduce the number of biopsies in patients with acute dysfunction of the kidney allograft.     

Utility of biopsy in kidney transplants with delayed graft function and acute dysfunction

Renal biopsy is currently the gold standard to assess the causes of renal allograft dysfunction. In the present study, we prospectively assessed the role of the renal allograft biopsy in the diagnosis and treatment of renal allograft dysfunction. Seven hundred and fifteen biopsies were performed in 399 patients. The anatomopathological results in group 1 (delayed graft function) were: 60.4% acute tubular necrosis, 17.6% acute rejection, 4.3% calcineurin inhibitor toxicity, and 17.7% other diagnoses; in group 2 (acute graft dysfunction): 42.3% acute rejection, 22% acute tubular necrosis, 8.4% calcineurin inhibitor toxicity, and 27.3% other diagnoses. Among patients with delayed graft function, 42.2% of biopsies led to a change in the treatment. In 60.5%, the biopsy of patients with acute dysfunction led to a change in the patient management. In our series, the result of the biopsy disagreed with the clinical diagnosis in 39.6% and 57.7% of cases, respectively. These results demonstrated that renal graft biopsy remains an indispensable tool for the accurate management of kidney transplant patients.     

Interleukin-6 expression after renal transplantation

BACKGROUND: Interleukin-6 (IL-6) is an inflammatory cytokine that plays a role in transplant rejection. We tested the hypothesis that IL-6 levels in serum or urine could be of value in predicting acute and chronic allograft rejection. Furthermore, we examined whether or not such levels reflected IL-6 expression in the kidney. METHODS: We measured IL-6 and IL-6 soluble receptor (IL-6sR) in serum and urine of 145 transplant patients and 20 normal controls. In parallel, we studied 108 renal biopsies. IL-6 was measured with a bioassay system using an IL-6 dependent cell line. IL-6sR was measured with enzyme-linked immunosorbent assay. The biopsies were examined for IL-6 and IL-6 receptor (IL-6R) expression with immunohistochemistry. RESULTS: Rejection episodes occurring within 2 months of transplantation were accompanied by elevated IL-6 concentrations in serum (17 +/- 4.8 pg/ml, P < 0.05) and urine (114 +/- 27 pg/ml, P < 0.005), compared to controls. These values returned towards baseline (0-5 pg/ml) after successful rejection treatment. The sensitivity of urine measurements was much higher (93%) than serum (54%). The specificity in serum (70%) and urine (60%) was reduced by infection, acute tubular necrosis, and antithymocyte globulin treatment. Serum and urine IL-6sR values did not correlate with rejection. In biopsy tissue, IL-6 and IL-6R were both elevated during rejection. Especially, mononuclear cells within the interstitial infiltrate stained positive. However, the amount of IL-6 positive cells did not correlate with peripheral IL-6 concentrations. CONCLUSIONS: Urine but not serum IL-6 values are sensitive indicators of rejection; however, they are confounded by infection, acute tubular necrosis, and certain antirejection treatments. These features limit their usefulness.      

Evaluation of posttransplantation soluble CD30 for diagnosis of acute renal allograft rejection

BACKGROUND: Posttransplantation measurement of soluble CD30 (sCD30) may be useful for identifying kidney graft recipients at risk of impending graft rejection in the early posttransplantation period. METHODS: We measured plasma sCD30 levels and evaluated the levels in relation to the diagnosis of rejection. RESULTS: Receiver operating characteristic curves demonstrated that on posttransplantation days 3 to 5, sCD30 allowed a differentiation of recipients who subsequently developed acute allograft rejection (n=25) from recipients with an uncomplicated course (n=20, P<0.0001) (area under the receiver operating characteristic curve 0.96, specificity 100%, sensitivity 88%) and recipients with acute tubular necrosis in the absence of rejection (n=11, P=0.001) (area under the receiver operating characteristic curve 0.85, specificity 91%, sensitivity 72%). CONCLUSIONS: sCD30 measured on posttransplantation days 3 to 5 offers a noninvasive means for differentiating patients with impending acute allograft rejection from patients with an uncomplicated course or with acute tubular necrosis.     

Early diagnosis of kidney transplant rejection and cyclosporin nephrotoxicity by urine cytology

A total of 2000 urine samples from 53 kidney transplant recipients were studied to develop a routine method for the early diagnosis of rejection and cyclosporin (CSA) nephrotoxicity in urine. New-Sternheimer staining and an immunocytochemical technique were used together with classical Papanicolaou staining to differentiate cells in the urine. After cell count and differentiation of second morning urine samples with New-Sternheimer and Papanicolaou stains, immunocytochemistry was performed using antibodies against the following antigens: CD2, CD4, CD8, CD25, CD71 (transferrin receptor), HLA-DR and cytokeratin (Lu-5). Cell counts were obtained for the positively-reacting cells per millilitre of urine. By New-Sternheimer and Papanicolaou staining, CSA nephrotoxicity was characterized by the predominance of proximal tubular cells. During rejection episodes, increased numbers of mononuclear cells and renal epithelial cells were found. Immunocytochemical analysis showed a significant increase in CD2-, CD4-, CD8-, CD25-, CD71-, and HLA-DR-positive epithelial cells and in the ratio HLA-DR/cytokeratin-positive epithelial cells in rejection. CD25-positive cells had the highest sensitivity and specificity for the diagnosis of rejection. Our urine cytology technique proved to be a useful and non-invasive method for the early diagnosis of rejection and CSA nephrotoxicity.     

Proteomic-based detection of urine proteins associated with acute renal allograft rejection

At present, the diagnosis of renal allograft rejection requires a renal biopsy. Clinical management of renal transplant patients would be improved by the development of non-invasive markers of rejection that can be measured frequently. This study sought to determine whether such candidate proteins can be detected in urine using mass spectrometry. Four patient groups were rigidly defined on the basis of allograft function, clinical course, and allograft biopsy result: acute clinical rejection group (n = 18), stable transplant group (n = 22), acute tubular necrosis group (n = 5), and recurrent (or de novo) glomerulopathy group (n = 5). Urines collected the day of the allograft biopsy were analyzed by mass spectrometry. As a normal control group, 28 urines from healthy individuals were analyzed the identical manner, as well as 5 urines from non-transplanted patients with lower urinary tract infection. Furthermore, sequential urine analysis was performed in patients in the acute clinical rejection and the stable transplant group. Three prominent peak clusters were found in 17 of 18 patients (94%) with acute rejection episodes, but only in 4 of 22 patients (18%) without clinical and histologic evidence for rejection and in 0 of 28 normal controls (P < 0.001). In addition, the presence or absence of these peak clusters correlated with the clinicopathologic course in most patients. Acute tubular necrosis, glomerulopathies, lower urinary tract infection, and cytomegalovirus viremia were not confounding variables. In conclusion, proteomic technology together with stringent definition of patient groups can detect urine proteins associated with acute renal allograft rejection. Identification of these proteins may prove useful as non-invasive diagnostic markers for rejection and the development of novel therapeutic agents.     

Limited value of 111-indium platelet scintigraphy in renal transplant patients receiving cyclosporine

Since the differential diagnosis between cyclosporine (CyA) nephrotoxicity and acute graft rejection is still a problem in clinical routine, we studied retrospectively the value of 111-indium (In) platelet scintigraphy in 53 patients immunosuppressed with CyA and prednisolone. Autologous platelets were labeled once per week. After daily gamma camera imaging, the platelet deposition in the graft was expressed as platelet-uptake ratio (PUR). The patients were monitored during the first 4-6 weeks after surgery. PUR values measured during an episode of graft dysfunction were compared to the histological diagnosis. The PUR of well-functioning and stable grafts measured 1.07 +/- 0.11 (mean +/- SD). The 111-In platelet scintigraphy failed to register acute interstitial rejection. The PUR values in episodes of chronic vascular rejection, of acute tubular necrosis due to prolonged ischemia times, of tubular CyA nephrotoxicity and of cytomegalovirus (CMV) infection did not differ from the PUR of well-functioning and stable grafts as well. The PUR was significantly increased to 1.48 +/- 0.26 because of a marked platelet deposition in the graft in episodes of acute vascular rejection. In 4 cases of microvascular CyA nephrotoxicity the same phenomenon of significantly increased PUR (1.33 +/- 0.18), could be encountered, too. Two of these 4 cases resembled the hemolytic uremic syndrome (HUS). The value of PUR measurement for diagnosis of acute vascular rejection and microvascular CyA nephrotoxicity together, was: sensitivity 0.62, specificity 0.95, predictive value of positive result 0.64, predictive value of negative result 0.94.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fine needle aspiration biopsy and cytology in renal transplantation

Fine needle aspiration biopsy with cytology provides a useful and easily repeated method of obtaining cell samples from a grafted kidney, enabling a more accurate diagnosis of rejection. The technique is simple to perform and is minimally invasive. It is easily repeated, daily if necessary, to evaluate events within the graft and the response to therapy. In addition to the findings of rejection (high total corrected incremental score and activated lymphocytes), both cyclosporin toxicity and acute tubular necrosis can be diagnosed. In the patient with a non-functioning graft with acute tubular necrosis, repeated fine needle aspiration biopsy may reveal early rejection. In rare cases, unusual graft infections have also been diagnosed by means of fine needle aspiration biopsy.     

A case of acute rejection with adenovirus infection after ABO-incompatible kidney transplantation

Abstract:  We report clinical and histopathologic findings of a case of acute rejection with adenovirus infection after kidney transplantation. A 63-yr-old woman with end-stage renal disease caused by lupus nephritis received an ABO-incompatible living kidney transplantation from her husband. On the 7th post-operative day (POD), she had fever, hematuria, and bladder irritation. Although she was treated with an antibiotic, the symptoms were not improved. We diagnosed adenovirus infection as positive with the urine shell vial method and blood PCR analysis. Cyclophosphamide was interrupted and immunoglobulin therapy was performed. However, urine output decreased and serum creatinine levels increased. An episode biopsy was performed on POD 20. We diagnosed acute antibody-mediated rejection. She was treated with plasma exchange for acute rejection and antiviral drug (rivabirin) for active adenovirus infection. However, the renal graft dysfunction was deemed irreversible and the renal graft was removed on POD 34. The graftectomy specimen showed acute rejection and acute tubular necrosis with adenovirus infection.     

Monoclonal analysis of fine-needle aspiration biopsy in kidney allografts

To evaluate changes in T-lymphocyte subsets and DR expression on tubular cells, 74 fine-needle allograft aspirates (FNAB) were evaluated in 31 patients with cadaver kidney transplants. Monoclonal antibodies against T helper CD4+, cytotoxic/suppressor CD8+, and HLA-DR were used with an indirect alkaline-phosphatase-staining technique. Cases with acute rejection (n = 11) showed a significant increase of CD8+: CD4+ ratio versus those with stable function (n = 21), acute tubular necrosis (n = 10) or CsA toxicity (n = 7) (ANOVA F = 10; P less than 0.01). Cases with chronic rejection or CMV infection showed no differences in the CD8+: CD4+ ratio with the other groups. DR expression on tubular cells was frequently found in cases of acute rejection, chronic rejection and CMV (73%, 66%, and 43% respectively), occasionally found in CsA toxicity (14%), but never seen in controls or ATN. Both tests, the CD8+: CD4+ ratio and the DR expression on tubular cells, had a high sensitivity and specificity in differentiating acute rejection versus controls, acute tubular necrosis, and CsA toxicity. When both tests are taken together no case without rejection showed a CD8+:CD4+ ratio greater than 1.6 and DR expression on tubular cells. Cases with acute rejection who lost the graft (n = 6) had a CD8+:CD4+ ratio significantly greater than those who responded to antirejection therapy (n = 5) (t = 2.9; P less than 0.05).     

The influence of primary non-function on the accuracy of ultrasound measurements in the diagnosis of renal allograft rejection

Daily ultrasonographic measurements of transplant cross-sectional area were used to quantify allograft swelling as a diagnostic test for acute rejection in a series of 120 renal transplants. Initial graft function (IF) occurred in 86 patients (72%) and primary non-function (PNF) occurred in the remaining 34 (28%). An increase in allograft cross-sectional area greater than or equal to 10% was defined as a positive ultrasound scan suggesting an acute rejection episode and was investigated by needle core biopsy. During periods of PNF, allografts with consistently negative ultrasound scans were submitted to needle core biopsy on a weekly basis. The diagnosis of rejection was based exclusively on the histological findings. In the IF group, agreement between ultrasound and histological diagnosis was good (k=0.63, sensitivity 81%, specificity 83%, positive predictive value 76%, negative predictive value 86% and overall accuracy 82%). In the PNF group, agreement between ultrasound and histology was only fair (k=0.46, sensitivity 77%, specificity 70%, positive predictive value 69%, negative predictive value 78% and overall accuracy 73%). It it concluded that a degree of allograft swelling is sometimes associated with acute tubular necrosis, and this makes ultrasound measurements of transplant size a less useful technique of monitoring kidneys with PNF.     

The L1 cell adhesion molecule is a potential biomarker of human distal nephron injury in acute tubular necrosis

The L1 cell adhesion molecule (CD171) is a multidomain membrane glycoprotein of the immunoglobulin superfamily. We evaluated its expression in human acute kidney injury and assessed its use as a tissue and urinary marker of acute tubular injury. Using immunohistochemical studies with antibodies to the extracellular or cytoplasmic domains, we compared L1 expression in normal kidneys in 24 biopsies taken from patients with acute tubular necrosis. L1 was found at the basolateral and the lateral membrane in all epithelial cells of the collecting duct in the normal kidney except for intercalated cells. In acute tubular necrosis, L1 lost its polarized distribution being found in both the basolateral and apical domains of the collecting duct. Further, it was induced in thick ascending limb and distal tubule cells. Apically expressed L1 found only when the cytoplasmic domain antibody was used in biopsy specimens of patients with acute tubular necrosis. The levels of urinary L1, normalized for creatinine, were significantly higher in all 24 patients with acute tubular necrosis compared to five patients with prerenal azotemia or to six patients with other causes of acute kidney injury. Our study shows that a soluble form of human L1 can be detected in the urine of patients with acute tubular necrosis and that this may be a marker of distal nephron injury.     

CsA顺序用药对移植肾早期功能的影响

１９９２年１月～１９９５年５月，分别对７８例及３２例肾移植患者术后立即应用ＡＬＧ和ＯＫＴ_３，随机选择８０例术后立即应用ＣｓＡ的患者为对照组，以了解ＣｓＡ顺序用药对移植肾早期功能的影响。结果显示：ＡＬＧ组和ＯＫＴ_３组急性排斥反应（ＡＲ）发生率分别为１１．５％和１２．５％，ＣｓＡ组为２３．８％（Ｐ＜０．０５），急性肾小管坏死（ＡＴＮ）ＡＬＧ组和ＯＫＴ_３组分别为５．１％和６．３％，ＣｓＡ组为１５．１％（Ｐ＜０．０５），移植肾功能３天正常率ＡＬＧ组和ＯＫＴ_３组分别为８３．３％和６８．８％，ＣｓＡ组为５７．５％（Ｐ＜０．０５）。证实ＣｓＡ顺序用药可有效地预防ＡＲ和ＡＴＮ的发生，促进移植肾功能的早期恢复。     

Diagnostic value of urinary enzyme determination in renal transplantation

Abstract  The measurement of enzyme activity in urine provides a sensitive assessment for renal tubular cell damage. The present study was undertaken to evaluate the clinical value of the determination of tubular brush-border-associated enzymes, alkaline phosphatase (AP), gamma-glutamyl transferase (GGT), leucine aminopeptidase (LAP), and dipeptidyl peptidase IV (DPP), of patients with normal graft function (NOR, n = 20), with acute tubular necrosis (ATN, n = ll), with an acute rejection episode ( ARE, n = 17) after transplantation, and of healthy persons ( n =20). The second urine of the morning was collected daily during the patients' stay in hospital. The enzyme activities were measured at 25 °C and were expressed as U/mmol creatinine. The enzymuria in NOR is higher than in healthy controls, but is still in the normal range. By 5 days after transplantation the initial increased excretion declines as the graft function improves. Elevated enzymuria (DPP 0.69 ± 0.56, AP 3.06 ± 3.24, GGT 4.16 ± 4.13, and LAP 1.39 ± 1.27) was observed during the rejection episodes. Two days before clinical diagnosis of rejection, the release of DPP-IV and GGT increases to double, and the AP and LAP increases to 3 times the value on the fourth day before rejection. Successful treatment of rejection coincided with a quick return by the third day of the rejection period to the previous enzyme distribution. In ATN no decrease of enzymuria occurs and the excretion is much higher than in ARE. Our method with the every day monitoring of kidney graft function offers the possibility for the early diagnosis of acute rejection.     

尸肾移植术后急性肾小管坏死的回顾性分析(附14例报告)

目的：探讨尸肾移植术后急性肾小管坏死（ATN）的发病因素和防治措施。方法：回顾性分析14例尸肾移植术后ATN患者的临床资料。结果：14例经过透析治疗，肾功能恢复正常。结论：ATN的发生与热缺血时间长、供肾灌注不良、低温保存不当等多因素有关。重视预防可能减少肾移植术后ATN的发生机会。一旦发生ATN，应尽早恢复透析，同时需预防急性排斥反应和其他并发症。     

Urinary fractalkine is a marker of acute rejection

Chemokines and their receptors play an important role in the development of allograft rejection through directing mononuclear cell invasion of the graft. To study whether chemokine assays in the urine could prove to be predictive of acute rejection, we measured the urinary excretion of several chemokines, including fractalkine, chemokine monokine induced by interferon-gamma, interferon-gamma-inducible protein 10, macrophage inflammatory protein-3 alpha, granzyme B, and perforin in 215 allograft recipients and in 80 healthy control subjects. The 67 patients with acute rejection had significantly higher levels of all urinary chemokines compared to the healthy controls or patients having chronic allograft nephropathy but with stable renal function. Only changes in urinary fractalkine differentiated patients with acute rejection from those with acute tubular necrosis. The 7 patients who lost their grafts had greater urinary fractalkine, interferon-gamma, and macrophage inflammatory protein-3 alpha concentrations than those patients with reversible acute rejection. The area under the receiver operating characteristic curve for fractalkine was the best indicator among all of the markers differentiating 39 patients diagnosed with steroid-resistant from the 28 patients with steroid-sensitive acute rejection and in predicting graft loss. Our study shows that measuring urinary fractalkine levels is a noninvasive approach for detecting acute rejection where high levels were associated with steroid-resistance and poor outcome.     

Biomarkers for the diagnosis of acute kidney injury

PURPOSE OF REVIEW: The identification of acute kidney injury relies on tests like blood urea nitrogen and serum creatinine that were identified and incorporated into clinical practice several decades ago. This review summarizes clinical studies of newer biomarkers that may permit earlier and more accurate identification of acute kidney injury. RECENT FINDINGS: The urine may contain sensitive and specific markers of kidney injury that are present due to either impaired tubular reabsorption and catabolism of filtered molecules or release of tubular cell proteins in response to ischemic or nephrotoxic injury. Many potential markers have been studied. Promising injury markers in the urine include N-acetyl-beta-D-glucosaminidase, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and interleukin-18. Serum cystatin C may be a better measure of glomerular filtration rate than serum creatinine or blood urea nitrogen. SUMMARY: New biomarkers of kidney injury and glomerular filtration rate hold the promise of substantially improving the diagnostic approach to acute kidney injury. Adequately powered clinical studies of multiple biomarkers are needed to qualify the biomarkers before they can be fully adopted in clinical practice. Once adopted, more sensitive biomarkers of acute kidney injury hold the potential to transform the care of patients with renal disease.     

Is patchy tubular injury a histopathological marker of acute rejection?

Abstract:  Renal allograft specimens often show patchy tubular injury (PTI), or patches of injured tubular sections. PTI reflects damage to the proximal tubules, and the histologic findings consist of tubular cell necrosis and tubular regeneration without tubulitis. Unlike acute tubular necrosis (ATN) in cadaveric donors, PTI can be observed in kidneys from living donors when there is no history of acute renal failure after transplantation. In this study, we examined the clinicopathological importance of PTI in acute rejection. Between April 2000 and May 2007, 2252 biopsies of living kidney grafts were performed at least one d after the transplant operation. Acute rejection was observed in 877 biopsies. Of these cases, 78 (8.9%) biopsies from 43 patients showed PTI. The severity of the PTI was graded semiquantitatively as follows: grade 1 cases had three or four damaged tubular sections, grade 2 cases had >5 sections, and grade 3 cases had >10 sections. The incidence of PTI was significantly higher in vascular rejection (VR) and antibody-mediated rejection (AMR) patients than in those experiencing tubulointerstitial rejection (TIR). The mean PTI score was significantly higher (2.00 ± 0.12) in VR than in TIR (1.39 ± 0.10) and AMR (1.68 ± 0.08) patients. The mean serum creatinine (sCr) at the time of biopsy was higher in VR patients than in AMR and TIR patients. Moreover, in VR patients, those with severer PTI developed higher sCr levels. These data suggest that PTI has a strong relationship with local ischemic damage delegated by VR, and the severity of PTI could be a practical histological marker in acute vascular rejection.