Allograft Biopsies Research Articles

Association of high intra-patient variability in tacrolimus exposure with calcineurin inhibitor nephrotoxicity in kidney transplantation

Tacrolimus intra-patient variability (IPV) is a novel predictive marker for long-term kidney transplantation outcomes. We examined the association between IPV and calcineurin inhibitor (CNI) nephrotoxicity and the impact of pharmacogenes on CNI nephrotoxicity and IPV. Among kidney transplant recipients at our hospital between January 2013 and December 2015, the records of 80 patients who underwent 1-year protocol renal allograft biopsy and agreed to donate blood samples for genetic analysis were retrospectively reviewed. The cohort was divided into the low and high IPV groups based on a coefficient variability cutoff value (26.5%). In multivariate analysis, the IPV group was involved in determining CNI nephrotoxicity (HR 4.55; 95% CI 0.05–0.95; p = 0.043). The 5-year graft survival was superior in the low IPV group than in the high IPV group (100% vs 92.4% respectively, p = 0.044). Analysis of the time above therapeutic range (TATR) showed higher CNI nephrotoxicity in the high IPV with high TATR group than in the low IPV with low TATR group (35.7% versus 6.7%, p = 0.003). Genetic analysis discovered that CYP3A4 polymorphism (rs2837159) was associated with CNI nephrotoxicity (HR 28.23; 95% CI 2.2–355.9; p = 0.01). In conclusion, high IPV and CYP3A4 polymorphisms (rs2837159) are associated with CNI nephrotoxicity.

Prospective quantitative study: Doppler ultrasound in the evaluation of chronic renal allograft disease and correlation with histopathological finding.

Renal allograft biopsy is the gold standard for diagnosing chronic allograft nephropathy, but noninvasive methods are needed to avoid unnecessary biopsies. Doppler ultrasonography, particularly the resistive index (RI), correlates with renal allograft dysfunction. This study aims to assess the relationship between renal sonographic parameters and biochemical parameters in diagnosing graft interstitial fibrosis. The study evaluated 60 renal allograft recipients for sonographic renal morphological features and Doppler indices. The estimated glomerular filtration rate (eGFR) was calculated, and cortical fibrosis after the biopsy was determined using the Banff score. Continuous variables like mean and SD were calculated, and categorical variables were reported using frequencies and proportions. Associations were examined using independent sample t-tests, χ 2tests, and multivariate regression analysis. The mean eGFR was 75.23±25.45ml/min/1.73m2. A significant correlation of eGFR with RI (r=0.341, P=0.008) was seen. A significant difference in mean RI (F=10.167; df=2,57; P<0.001) was seen among the histological grades of fibrosis. Among the histological grades of fibrosis, significant differences in RI among mild and moderate (S.E. 0.033, P=0.043), mild and severe (S.E. 0.026, P=0.001) as well as moderate and severe (S.E. 0.036, P=0.029) was seen. Doppler was able to noninvasively predict allograft fibrosis and could be used as a complementary imaging tool during the follow-up of renal allograft patients. Future research is needed to improve evidence, diagnostic criteria, guidelines, and long-term impact.

Risk Factors and Causality of Early Graft Loss in Kidney Transplanted Patients in Northwestern Iran: A 10-Year Retrospective Study

Background: Early graft loss (EGL) is one of the rare complications of kidney transplantation. Several factors play a role in the occurrence of EGL in kidney transplant recipients, which must be identified and limited. Objectives: This ten-year retrospective study was conducted in a single center on 32 kidney transplant recipients with EGL to determine the reasons for and risk factors of kidney transplant rejection in Iran. Methods: This descriptive-analytical study’s population included 605 kidney transplant recipients receiving kidneys during the last ten years in our center. The diagnosis of EGL was based on renal allograft biopsy examination and primary clinical complications, including a rapid increase in serum creatinine. The age, gender, blood group, and rhesus (Rh) of both donors and recipients, as well as the kinship between the donor and recipient (relative and non-relative), right/left-sided living donor/recipient kidneys, primary kidney disease, the presence of underlying disease in the recipient, dialysis duration, the year of kidney transplantation, transplant survival time, patient survival time, and complications (surgery and others) were gathered. The data were analyzed using SPSS version 18. Results: In this study, 32 out of 605 kidney transplant recipients (5.28%) experienced EGL (53.1% male and 46.9% female, average age of 41.12 years). The duration of kidney function after transplantation was 5.56 ± 0.13 days. The transplanted kidneys were functional between 72 hours and one week after transplantation in 34.4% of the patients. The causes of EGL were found to be tissue rejection in 31.3% of the patients and vascular thrombosis and hyperacute rejection in 21.8%. Nephrectomy occurred in 41% of the patients, and 43.75% died because of a heart attack. Conclusions: Our findings supported previous studies' results, suggesting that EGL is associated with receiving an incompatible kidney transplant and surgery-related complications, including bleeding and thrombosis.

Clinical Outcomes of Monoclonal Gammopathy of Renal Significance Without Detectable Clones

Monoclonal gammopathy of renal significance (MGRS) is characterized by monoclonal immunoglobulin deposition in kidneys. However, monoclonal immunoglobulin and responsible clone(s) are not always detectable. Treatment response and kidney outcome of MGRS without detectable clones remain unclear. In this single-center, retrospective cohort study, we identified MGRS without detectable clones from our biopsy repository between 2010 and 2022. We investigated the correlations between treatment regimens and kidney outcomes defined by proteinuria and estimated glomerular filtration rate (eGFR), and the impact of repeat kidney biopsy. Our study cohort included 29 cases (27 native kidney and 2 transplant allograft biopsies) of MGRS without detectable clones. At diagnosis, median serum creatinine was 1.8 mg/dl (interquartile range [IQR] 1.3-2.7), with proteinuria 4.6 g/gCr (IQR 2.3-7.9). Treatment regimens were variable: 6 (21%) received conservative therapy, 13 (45%) received plasma cell clone-directed therapy, 8 (28%) received lymphocytic clone-directed therapy, and 2 (7%) received nonclone-directed immunosuppressive therapy. Of 24 patients with proteinuria >0.5 g/gCr at diagnosis, 9 (38%) and 6 (25%) achieved complete response (CR) and partial response (PR), respectively. If interstitial fibrosis and tubular atrophy (IFTA) was >50% at the initial biopsy, less proportion of patients achieved CR. Six of 7 repeat biopsies showed progression of chronic changes (e.g., IFTA) but provided limited information on treatment response. Treatment regimens and outcomes of MGRS without detectable clones were extremely variable. Repeat biopsy provided limited information to assess disease activity or the need for additional treatment. More sensitive tools are needed to detect clones and to assess treatment response.

Evolution of human kidney allograft pathology diagnostics through 30 years of the Banff classification process.

The second half of the previous century witnessed a tremendous rise in the number of clinical kidney transplants worldwide. This activity was, however, accompanied by many issues and challenges. An accurate diagnosis and appropriate management of causes of graft dysfunction were and still are, a big challenge. Kidney allograft biopsy played a vital role in addressing the above challenge. However, its interpretation was not standardized for many years until, in 1991, the Banff process was started to fill this void. Thereafter, regular Banff meetings took place every 2 years for the past 30 years. Marked changes have taken place in the interpretation of kidney allograft biopsies, diagnosis, and classification of rejection and other non-rejection pathologies from the original Banff 93 classification. This review attempts to summarize those changes for increasing the awareness and understanding of kidney allograft pathology through the eyes of the Banff process. It will interest the transplant surgeons, physicians, pathologists, and allied professionals associated with the care of kidney transplant patients.

Outcomes of asymptomatic histologic pyelonephritis of kidney transplant.

Urinary Tract Infections are the most common post-transplant infection and can have varied presentations. This study aimed to describe the outcomes of kidney transplant recipients with asymptomatic histologic pyelonephritis on allograft biopsy. Histologic Pyelonephritis was defined as neutrophil cast or neutrophilic tubulitis, interstitial infiltrates with predominant neutrophils, and no evidence of rejection or glomerulonephritis on biopsy. The study included 123 kidney transplant recipients, of whom 95 underwent protocol biopsies, and 28 had biopsies for elevated creatinine within the first 2 years of a kidney transplant. The mean age of the cohort was 55.3 years, with 52% females and 78% deceased donor transplants. The risk factors for asymptomatic histologic pyelonephritis were recipient female sex (OR 1.89, 1.3-2.7, diabetes mellitus (OR 2.479, 1.687-3.645), and deceased donation (OR 1.69, 1.098-2.63). The incidence of asymptomatic pyelonephritis on protocol biopsy was 1.7%, with 52% having positive urine cultures and Escherichia coli being the most common bacteria. Subjects with asymptomatic pyelonephritis had inferior graft survival compared to the matched cohort HR 1.88 (1.06-3.35), p=.0281. In addition, of these 123 subjects, 68 (55%) subsequently developed pyelonephritis, and 34 subjects had pyelonephritis within 6 months after this episode. Subjects with recurrent infections exhibited lower survival HR 2.86 (1.36-6.02) and a trend toward higher rejection risk. Asymptomatic histologic pyelonephritis can occur in kidney transplant recipients and is associated with inferior graft survival.

Discrepancy Analysis between Histology and Molecular Diagnoses in Kidney Allograft Biopsies: A Single-Center Experience.

Histology diagnosis is essential for the monitoring and management of kidney transplant patients. Nowadays, the accuracy and reproducibility of histology have been criticized when compared with molecular microscopy diagnostic system (MMDx). Our cohort included 95 renal allograft biopsies with both histology and molecular diagnoses. Discrepancies between histology and molecular diagnosis were assessed for each biopsy. Among the 95 kidney allograft biopsies, a total of 6 cases (6%) showed clear (n = 4) or borderline (n = 2) discrepancies between histology and molecular diagnoses. Four out of the six (67%) were cases with pathologically and clinically confirmed active infections that were diagnosed as mild to moderate T-cell-mediated rejection (TCMR) with MMDx. Two cases showed pathological changes that were not sufficient to make a definitive diagnosis of active rejection via histology, while MMDx results showed antibody-mediated rejection (ABMR). In addition, there were six cases with recurrent or de novo glomerular diseases diagnosed only via histology. All other biopsy results were in an agreement. Our results indicate that histology diagnosis of kidney allograft biopsy is superior to molecular diagnosis in the setting of infections and glomerular diseases; however, MMDx can provide helpful information to confirm the diagnosis of active ABMR.

Recurrent Immunoglobulin A Nephropathy after Kidney Transplant—An Updated Review

Immunoglobulin A nephropathy (IgAN) is the commonest glomerulonephritis worldwide, a category that represents the third most frequent cause of end-stage kidney disease (ESKD) in the United States. Kidney transplantation remains the optimal treatment of ESKD, and yet the prospects of IgAN recurrence post-transplant dampens the enthusiasm for living kidney donation in some instances, in addition to limiting the longevity of the kidney allograft. Moreover, the lack of a standardized method for detecting IgAN recurrence, since not all centers perform protocol allograft biopsies, has led to an underestimation of the extent of the issue. The pathogenesis of de novo IgAN remains conjectural, let alone the pathways for recurrent disease, but is increasingly recognized as a multi-hit injury mechanism. Identification of recurrent disease rests mainly on clinical symptoms and signs (e.g., hematuria, proteinuria) and could only be definitively proven with histologic evidence which is invasive and prone to sampling error. Treatment had relied mainly on nonspecific goals of proteinuria reduction, and in some cases, immunosuppression for active, crescentic disease. More recently, newer targets have the potential to widen the armamentarium for directed therapies, with more studies on the horizon. This review article provides an update on recurrent IgAN post-transplant.

Posttransplant Thrombotic Microangiopathy: Unraveling a Mystery

A 24 year old lady who was diagnosed with chronic kidney disease stage 5 in 2016 underwent a pre-emptive live related renal transplant in the same year. She had kidney allograft dysfunction and eventually lost the transplant kidney in 2019 requiring hemodialysis. She underwent a deceased donor renal transplant in February 2022. She developed allograft dysfunction with a creatinine of 2.5 mg/dl in October 2022, and a renal allograft biopsy subsequently showed Thrombotic microangiopathy, arteriolar form. There were no features of rejection in the biopsy and Donor specific antibody done by Luminex lysate method was negative. Her Single antigen bead done subsequently was also negative. CMV DNA PCR was not detectable. Tacrolimus was switched to Cyclosporine, however her allograft function continued to worsen. Complement mutation analysis was negative and acquired complement defects were also not detected. Subsequently, Single antigen bead for non HLA antibodies showed positivity for MICA antibodies. She underwent 7 sessions of plasmapheresis and her renal functions did not improve and her creatinine continued to increase to 4.2 mg/dl. Complement activating assay for these MICA antibodies was positive. She was treated with two doses of 300 mg Eculizumab in December 2022, her allograft functions in February 2023 have improved to 2 mg/dl. This case highlights the extensive evaluation for post transplant TMA, the use of non HLA antibody assays and complement activating assays of these antibodies to decide on appropriate use of Eculizumab for salvaging transplant allograft.

Histopathological diagnoses revealed by indication-based renal allograft biopsies: a retrospective analysis

Objectives: Although there have been several advances in post-solid organ transplantation immunosuppression medications over the last two decades, the long-term survival of renal allografts did not significantly improve. Renal allograft biopsy is a helpful tool for determining the cause of graft dysfunction and adjusting patient management. Methods: Patients who received kidney transplantation and underwent allograft biopsy in Istinye University Hospital between January 2017 and January 2023 constituted the target population of this study. Demographic parameters, clinical data and biopsy indications, and histopathological assessment results of the patients were retrospectively analyzed. Results: Overall, 74 patients were included. The histopathology results included acute T-Cell mediated rejection (TCMR) (n = 15, 20%), tubular atrophy/chronic allograft nephropathy (IFTA) (n = 11, 15%), calcineurin inhibitor (CNI) toxicity (n = 2, 3%), chronic antibody-mediated rejection (ABMR) (n = 2, 3%), borderline pathology (n = 10, 13.5%), normal histology (n = 5, 6.5%), transplant glomerulopathy (TG) (n = 5, 6.5%), acute ABMR (n = 4, 5%), acute tubular necrosis (n = 7, 9%), polyomavirus nephropathy (n = 3, 4%) and non-specific changes (n = 10, 13.5%). The C4d was positive in 12% (n = 9) of the graft biopsies. In 73% (n = 54) of cases, the treatment strategy was changed based on biopsy results. Among all patients, 19 (25.6%) lost their grafts during follow-up. Conclusions: According to the histopathological analysis results, acute TCMR, IFTA, and borderline pathology were the most common causes of renal graft dysfunction. Renal allograft biopsy led to a remarkable change in treatment strategies in a significant number of cases.

Banff Human Organ Transplant Consensus Gene Panel for the Detection of Antibody Mediated Rejection in Heart Allograft Biopsies.

The molecular refinement of the diagnosis of heart allograft rejection based on whole-transcriptome analyses faces several hurdles that greatly limit its widespread clinical application. The targeted Banff Human Organ Transplant gene panel (B-HOT, including 770 genes of interest) has been developed to facilitate reproducible and cost-effective gene expression analysis of solid organ allografts. We aimed to determine in silico the ability of this targeted panel to capture the antibody-mediated rejection (AMR) molecular profile using whole-transcriptome data from 137 heart allograft biopsies (71 biopsies reflecting the entire landscape of histologic AMR, 66 non-AMR control biopsies including cellular rejection and non-rejection cases). Differential gene expression, pathway and network analyses demonstrated that the B-HOT panel captured biologically and clinically relevant genes (IFNG-inducible, NK-cells, injury, monocytes-macrophage, B-cell-related genes), pathways (interleukin and interferon signaling, neutrophil degranulation, immunoregulatory interactions, endothelial activation) and networks reflecting the pathophysiological mechanisms underlying the AMR process previously identified in whole-transcriptome analysis. Our findings support the potential clinical use of the B-HOT-gene panel as a reliable proxy to whole-transcriptome analysis for the gene expression profiling of cardiac allograft rejection.

O32 Bioinformatic segregation of chimeric libraries enables accurate donor HLA typing from allograft biopsies by ONT

O32 Bioinformatic segregation of chimeric libraries enables accurate donor HLA typing from allograft biopsies by ONT

Immune monitoring of prevalent kidney transplant recipients using Torque Teno Virus: Protocol for a single-centre prospective cohort study

IntroductionKidney transplant recipients (KTRs) suffer from immunosuppression-related adverse events (iRAEs), such as infections and malignancy from chronic immunosuppression, but are also at risk of graft loss from rejection with underimmunosuppression....

Identification of Renal Transplantation Rejection Biomarkers in Blood Using the Systems Biology Approach.

Renal transplantation plays an essential role in the quality of life of patients with end-stage renal disease. At least 12% of the renal patients receiving transplantations show graft rejection. One of the methods used to diagnose renal transplantation rejection is renal allograft biopsy. This procedure is associated with some risks such as bleeding and arteriovenous fistula formation. In this study, we applied a bioinformatics approach to identify serum markers for graft rejection in patients receiving a renal transplantation. Transcriptomic data were first retrieved from the blood of renal transplantation rejection patients using the GEO database. The data were then used to construct the protein-protein interaction and gene regulatory networks using Cytoscape software. Next, network analysis was performed to identify hub-bottlenecks, and key blood markers involved in renal graft rejection. Lastly, the gene ontology and functional pathways related to hub-bottlenecks were detected using PANTHER and DAVID servers. In PPIN and GRN, SYNCRIP, SQSTM1, GRAMD1A, FAM104A, ND2, TPGS2, ZNF652, RORA, and MALAT1 were the identified critical genes. In GRN, miR-155, miR17, miR146b, miR-200 family, and GATA2 were the factors that regulated critical genes. The MAPK, neurotrophin, and TNF signaling pathways, IL-17, and human cytomegalovirus infection, human papillomavirus infection, and shigellosis were identified as significant pathways involved in graft rejection. The above-mentioned genes can be used as diagnostic and therapeutic serum markers of transplantation rejection in renal patients. The newly predicted biomarkers and pathways require further studies.

Molecular immune monitoring in kidney transplant rejection: a state-of-the-art review.

Although current regimens of immunosuppressive drugs are effective in renal transplant recipients, long-term renal allograft outcomes remain suboptimal. For many years, the diagnosis of renal allograft rejection and of several causes of renal allograft dysfunction, such as chronic subclinical inflammation and infection, was mostly based on renal allograft biopsy, which is not only invasive but also possibly performed too late for proper management. In addition, certain allograft dysfunctions are difficult to differentiate from renal histology due to their similar pathogenesis and immune responses. As such, non-invasive assays and biomarkers may be more beneficial than conventional renal biopsy for enhancing graft survival and optimizing immunosuppressive drug regimens during long-term care. This paper discusses recent biomarker candidates, including donor-derived cell-free DNA, transcriptomics, microRNAs, exosomes (or other extracellular vesicles), urine chemokines, and nucleosomes, that show high potential for clinical use in determining the prognosis of long-term outcomes of kidney transplantation, along with their limitations.

Evaluation of the Modified Oxford Score in Recurrent IgA Nephropathy in North American Kidney Transplant Recipients: The Banff Recurrent Glomerulonephritis Working Group Report.

The modified Oxford classification mesangial and endocapillary hypercellularity, segmental sclerosis, interstitial fibrosis/tubular atrophy, and the presence of crescents (MEST-C) of immunoglobulin A nephropathy (IgAN) was recently shown to be a predictor of graft failure in Asians with recurrent IgAN. We aimed to validate these findings in a cohort from North American centers participating in the Banff Recurrent Glomerulopathies Working Group. We examined 171 transplant recipients with end-stage kidney disease because of IgAN; 100 of them with biopsy-proven recurrent IgAN (57 of them had complete MEST-C scores) and 71 with no recurrence. IgAN recurrence, which was associated with younger age at transplantation ( P = 0.012), strongly increased the risk of death-censored graft failure (adjusted hazard ratio, 5.10 [95% confidence interval (CI), 2.26-11.51]; P < 0.001). Higher MEST-C score sum was associated with death-censored graft failure (adjusted hazard ratio, 8.57 [95% CI, 1.23-59.85; P = 0.03] and 61.32 [95% CI, 4.82-779.89; P = 0.002] for score sums 2-3 and 4-5 versus 0, respectively), and so were the single components endocapillary hypercellularity, interstitial fibrosis/tubular atrophy, and crescents ( P < 0.05 each). Overall, most of the pooled adjusted hazard ratio estimates associated with each MEST-C component were consistent with those from the Asian cohort (heterogeneity I2 close to 0%, and P > 0.05). Our findings may validate the prognostic usefulness of the Oxford classification for recurrent IgAN and support the inclusion of the MEST-C score in allograft biopsies diagnostic reports.

Utilization of donor-derived Cell-Free DNA in pediatric kidney transplant recipients: A single center study.

Forty-two pediatric kidney transplant patients were enrolled between February 2020 and August 2021. Dd-cfDNA was tested before and after biopsy/rejection treatment. There was a total of 61 allograft biopsies (44 for-cause, 17 surveillance). Graft rejection was found in 35/61 biopsies. Rejection was more common in basiliximab induction compared to rATG (77.1% vs. 22.9%, p = .0121). Median dd-cfDNA was higher in those with rejection (1.2% [0.34-3.12] vs. 0.24% [0.08-0.78], p < .0001). Dd-cfDNA was highest in biopsies with AMR and mixed AMR/TCMR. In addition, dd-cfDNA in basiliximab induction was higher compared to rATG (0.92% [0.27-1.8] vs. 0.26% [0.08-2], p = .0437). Median change in dd-cfDNA after rejection treatment was -0.57% (-1.67 to 0.05). Median time to dd-cfDNA <1% post-rejection treatment was 8.5 days (3.0-19.5). Dd-cfDNA in AMR was higher compared to TCMR or mixed rejection, and levels remained higher in AMR after treatment. In surveillance biopsies, 4/17 had rejection. Median dd-cfDNA was not different in those with versus without rejection (0.48% vs. 0.28%, p = .2342). Those without rejection all had dd-cfDNA <1%. In those with rejection, only one patient had dd-cfDNA >1%, and all had TCMR. Our findings support dd-cfDNA as a useful indicator of graft rejection and response to treatment. Additional studies are needed to determine the role of dd-cfDNA in graft health surveillance.

Acute tubulointerstitial nephritis possibly caused by vedolizumab for ulcerative colitis in a kidney transplant recipient: A case report.

Vedolizumab, which is used to effectively treat ulcerative colitis (UC), is a humanized monoclonal antibody that specifically inhibits α4β7 integrin on lymphocytes and prevents lymphocyte migration into the intestinal tissues. Herein, we report a case of acute tubulointerstitial nephritis (ATIN) probably caused by vedolizumab in a kidney transplant recipient (KR) with UC. Approximately 4 years after kidney transplantation, the patient developed UC and was treated initially with mesalazine. Treatment continued with the addition of infliximab later; however, he was hospitalized because of poor symptom control and treated with vedolizumab. His graft function declined rapidly after vedolizumab was administered. Allograft biopsy revealed ATIN. Since no evidence of graft rejection was found, vedolizumab-associated ATIN was diagnosed. The patient was treated with steroids, and his graft function improved. Unfortunately, he finally underwent total colectomy considering that UC was refractory to medical treatment. Previously, cases of vedolizumab-induced acute interstitial nephritis have been reported; however, none were associated with KRs. This is the first report of ATIN in KR which was possibly induced by vedolizumab.

Significance of Arterial Spin Labeling for Reducing Biopsies in Patients With Kidney Allograft Dysfunction.

Although biopsy is often entailed for managing patients with kidney allograft dysfunction, it is associated with potential complications of severe hemorrhage. Arterial spin labeling (ASL) is a non-invasive technique that assesses tissue perfusion. To assess the utility of ASL for the discrimination of patients with post-transplant allograft dysfunction who do not need biopsy from those who need. Prospective. Forty-six patients (34 males/12 females, aged 38.8 ± 9.5 years) with kidney allograft dysfunction, including 31 in which biopsy directly lead to changes in management (NECESSARY group) and 15 in which clinical management did not alter after biopsy (UNNECESSARY group). 3.0 T and 3D fast-spin echo sequence. All patients underwent both ASL scan and biopsies. The serum creatinine, proteinuria, pathologic results, and cortical ASL readings were obtained and compared between the two groups. Chi-square test, independent student t-test, Mann-Whitney U test, receiver-operating characteristic curve. A two-tailed P < 0.05 denoted statistical significance. The NECESSARY group presented with significantly elevated serum creatinine as compared with the UNNECESSARY group (1.87 ± 0.56 mg/dL vs. 1.31 ± 0.37 mg/dL). The acute composite score was significantly higher in the NECESSARY group than that in the UNNECESSARY group (7 [4-8] vs. 1 [0-2]). Cortical ASL in the NECESSARY group was significantly decreased as compared with the UNNECESSARY group (108.06 [69.96-134.92] mL/min/100 g vs. 153.48 [113.19-160.37] mL/min/100 g). Serum creatinine differentiated UNNCESSARY group from the NECESSARY group with an area under the curve (AUC) and specificity of 0.79 and 54.84%, respectively. By comparison, the cortical ASL yielded an AUC of 0.75 and a specificity of 70.97%. Notably, the specificity was increased to 90.30% by combined use of serum creatinine and cortical ASL. The combined use of ASL and serum creatinine yielded a high specificity for selecting patients who may not need allograft biopsy. 2 TECHNICAL EFFICACY: Stage 3.

Importance of Follow-Up Biopsies in the Prediction of Renal Allograft Survival Following Polyomavirus-Associated Nephropathy.

Allograft biopsy is the gold standard for diagnosing polyomavirus-associated nephropathy. We aimed to establish the effects of histopathologic findings proposed by the Banff Polyomavirus Working Group on graft outcome. We also aimed to understand the clinical importance of follow-up biopsies for patients with polyomavirus-associated nephropathy. Our study included 22 patients with polyomavirus-associated nephropathy. All biopsies were classified according to the latest Banff Polyomavirus Working Group classification. Follow-up biopsies of all patients were evaluated in detail. The mean interval between polyomavirus-associated nephropathy and transplant was 10 ± 1.6 months. Of 22 patients, biopsy revealed stage 1 in 3 (13.6%), stage 2 in 17 (77.3%), and stage 3 in 2 patients (9.1%). Fourteen patients (63.6%) had polyomavirus viral load 3, 5 (22.7%) had polyomavirus viral load 2, and 3 had polyomavirus viral load 1. Among patients included in analyses, 18.2% had antibody-mediated rejection and 27.2% had T-cell-mediated rejection simultaneously with polyomavirus-associated nephropathy. Graft loss increased with increasing polyomavirus-associated nephropathy class and polyomavirus viral load (P = .015 and P = .002, respectively). The mean time of graft survival decreased with increasing degree of tubulitis, interstitial inflammation, plasma infiltration, and neutrophil infiltration. Patients with interstitial fibrosis, glomerular polyoma, and cortical plus medullar involvement showed earlier graft loss. Follow-up biopsies showed that diffuse interstitial fibrosis or persistent inflam-mation negatively influenced graft loss. The Banff Polyomavirus Working Group's schema significantly correlated with graft outcome. Early detection of polyomavirus-associated nephro-pathy and subsequent detection of persistent inflammation and interstitial fibrosis and tubular atrophy in follow-up biopsies and modification of immunosuppressive therapy can successfully prevent graft loss.