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Jeerararuensak W, Taweemonkongsap T, Larpparisuth N, Tantranont N, Chotikawanich E, Jitpraphai S, Woranisarakul V, Hansomwong T. Color Doppler Guided in Early Renal Allograft Biopsy: A Safer and Non-Inferior Technique. Transplant Proc 2023; 55:2385-2391. [PMID: 37872065 DOI: 10.1016/j.transproceed.2023.09.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Revised: 08/07/2023] [Accepted: 09/22/2023] [Indexed: 10/25/2023]
Abstract
BACKGROUND This study compared a novel technique for renal allograft biopsy, color Doppler ultrasound-guided biopsy (CDUS-Bx), with routine ultrasound-guided biopsy (RUS-Bx). METHODS A retrospective review was conducted on 111 patients, with 42 undergoing CDUS-Bx and 69 undergoing RUS-Bx. Urologists used an 18-gauge automatic spring-loaded biopsy needle for all procedures. CDUS-Bx tissue collection was guided by identifying renal vessels with color Doppler mode. RESULTS Overall, the adequacy rate was 90.1%, with a higher number of glomeruli obtained in the CDUS-Bx group (25.6 ± 10.3 vs. 20.6 ± 11.3, P = .008). Acute tubular necrosis was the most frequent pathological diagnosis, with a higher prevalence in the CDUS-Bx group (69% vs 40.6%). T cell-mediated rejection had a lower incidence in the CDUS-Bx group (4.8% vs 21.7%), and antibody-mediated rejection was comparable between the 2 groups. The most common complication was microscopic hematuria, which was significantly less frequent in the CDUS-Bx group (48.7% vs 70.1%, P = .028), but there was no significant difference in the rate of gross hematuria between CDUS-Bx and RUS-Bx (11.9% vs 11.6%, P = .961). The number of cores was the only predictor of adequate biopsy, with a 93.2% adequacy rate after 3 cores of allograft biopsy. Multivariate analysis revealed that only the guiding type, CDUS-Bx, was associated with less microscopic hematuria (adjusted odds ratio 0.325, P = .018). CONCLUSIONS Color Doppler ultrasound-guided biopsy had comparable tissue adequacy to RUS-Bx, with a lower incidence of microscopic hematuria. These findings suggest that CDUS-Bx may be a safe and effective alternative to RUS-Bx for allograft biopsy.
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Affiliation(s)
- Wasin Jeerararuensak
- Division of Urology, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Tawatchai Taweemonkongsap
- Division of Urology, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Nuttasith Larpparisuth
- Division of Nephrology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Ngoentra Tantranont
- Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Ekkarin Chotikawanich
- Division of Urology, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Siros Jitpraphai
- Division of Urology, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Varat Woranisarakul
- Division of Urology, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Thitipat Hansomwong
- Division of Urology, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
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Mubarak M, Raza A, Rashid R, Shakeel S. Evolution of human kidney allograft pathology diagnostics through 30 years of the Banff classification process. World J Transplant 2023; 13:221-238. [PMID: 37746037 PMCID: PMC10514746 DOI: 10.5500/wjt.v13.i5.221] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 06/05/2023] [Accepted: 06/12/2023] [Indexed: 09/15/2023] Open
Abstract
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.
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Affiliation(s)
- Muhammed Mubarak
- Department of Histopathology, Sindh Institute of Urology and Transplantation, Karachi 74200, Sindh, Pakistan
| | - Amber Raza
- Department of Nephrology, Sindh Institute of Urology and Transplantation, Karachi 74200, Sindh, Pakistan
| | - Rahma Rashid
- Department of Histopathology, Sindh Institute of Urology and Transplantation, Karachi 74200, Sindh, Pakistan
| | - Shaheera Shakeel
- Department of Histopathology, Sindh Institute of Urology and Transplantation, Karachi 74200, Sindh, Pakistan
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Liang P, Yuan G, Li S, He K, Peng Y, Hu D, Li Z, Ma Z, Xu C. Non-invasive evaluation of the pathological and functional characteristics of chronic kidney disease by diffusion kurtosis imaging and intravoxel incoherent motion imaging: comparison with conventional DWI. Br J Radiol 2023; 96:20220644. [PMID: 36400040 PMCID: PMC10997028 DOI: 10.1259/bjr.20220644] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Revised: 10/26/2022] [Accepted: 11/06/2022] [Indexed: 11/20/2022] Open
Abstract
OBJECTIVE To explore the diagnostic performance of diffusion kurtosis imaging (DKI) and incoherent intravoxel movement (IVIM) in evaluating the clinical and pathological characteristics in chronic kidney disease (CKD) compared to conventional diffusion-weighted imaging (DWI). METHODS Forty-nine CKD patients and 24 healthy volunteers were included in this retrospective study from September 2020 to September 2021. All participants underwent MRI examinations before percutaneous renal biopsy. Coronal T2WI, axial T1WI and T2WI, and DWI (including IVIM and DKI) sequences obtained in one scan. We measured the apparent diffusion coefficient (ADC), true diffusion coefficient (Dt), pseudo-diffusion coefficient (Dp), perfusion fraction (fp), mean kurtosis (MK), and mean diffusivity (MD) values. One-way analysis of variance, correlation analysis, and receiver operating characteristic curve analysis were used in our study. RESULTS Cortex and medulla ADC, MK, Dt, fp were significantly different between the healthy volunteers and CKD stages 1-2 (all p < 0.05). All diffusion parameters showed significant differences between CKD stages 1-2 and CKD stages 3-5 (all p < 0.05). Except for the uncorrelation between MDMedulla and vascular lesion score, all other diffusion parameters were low-to-moderately related to clinical and pathological indicators. fpMedulla was the best parameter to differentiate healthy volunteers from CKD stages 1-2. MKCortex was the best parameter to differentiate CKD stages 1-2 from that CKD stages 3-5. CONCLUSION Renal cortex and medulla fp, Dt, and MK can provide more valuable information than ADC values for the evaluation of clinical and pathological characteristics of CKD patients, and thus can provide auxiliary diagnosis for fibrosis assessment and clinical management of CKD patients. ADVANCES IN KNOWLEDGE IVIM and DKI can provide more diagnostic valuable information for CKD patients than conventional DWI.
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Affiliation(s)
- Ping Liang
- Department of Radiology, Tongji Hospital, Tongji Medical
College, Huazhong University of Science and Technology,
Wuhan, China
| | - Guanjie Yuan
- Department of Radiology, Tongji Hospital, Tongji Medical
College, Huazhong University of Science and Technology,
Wuhan, China
| | - Shichao Li
- Department of Radiology, Tongji Hospital, Tongji Medical
College, Huazhong University of Science and Technology,
Wuhan, China
| | - Kangwen He
- Department of Radiology, Tongji Hospital, Tongji Medical
College, Huazhong University of Science and Technology,
Wuhan, China
| | - Yang Peng
- Department of Radiology, Tongji Hospital, Tongji Medical
College, Huazhong University of Science and Technology,
Wuhan, China
| | - Daoyu Hu
- Department of Radiology, Tongji Hospital, Tongji Medical
College, Huazhong University of Science and Technology,
Wuhan, China
| | - Zhen Li
- Department of Radiology, Tongji Hospital, Tongji Medical
College, Huazhong University of Science and Technology,
Wuhan, China
| | - Zufu Ma
- Department of Nephrology, Tongji Hospital, Tongji Medical
College, Huazhong University of Science and Technology,
Wuhan, China
| | - Chuou Xu
- Department of Radiology, Tongji Hospital, Tongji Medical
College, Huazhong University of Science and Technology,
Wuhan, China
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Park WY, Kim Y, Paek JH, Jin K, Han S. Clinical significance of serum galactose-deficient immunoglobulin A1 for detection of recurrent immunoglobulin A nephropathy in kidney transplant recipients. Kidney Res Clin Pract 2021; 40:317-324. [PMID: 33866766 PMCID: PMC8237123 DOI: 10.23876/j.krcp.20.183] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Accepted: 12/28/2020] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Recurrent glomerulonephritis (GN) is a common cause of allograft loss in kidney transplantation (KT), the most frequent of which is immunoglobulin A (IgA) nephropathy (IgAN). Galactose-deficient IgA1 (Gd-IgA1) plays a major role in the pathophysiology of IgAN, but the association between Gd-IgA1 and recurrent IgAN in kidney transplant recipients (KTRs) is uncertain. We aimed to evaluate the efficacy of Gd-IgA1 for prediction of recurrent IgAN and graft and patient survival according to Gd-IgA1 level. METHODS We enrolled 27 KTRs who underwent allograft biopsy between 2009 and 2016 and measured the serum Gd-IgA1 level of each KTR. We divided the patients into two groups: nonrecurrent IgAN (patients with IgAN prior to KT who were not diagnosed with recurrent IgAN) and recurrent IgAN (patients with IgAN prior to KT who were diagnosed with recurrent IgAN). RESULTS The mean serum Gd-IgA1 level was significantly higher in the recurrent IgAN group than in the nonrecurrent IgAN group (6,419 ± 3,675 ng/mL vs. 3,381 ± 2,844 ng/mL, p = 0.02). The cutoff value of serum Gd-IgA1 in receiver operating characteristic curve analysis was 4,338 ng/mL (area under the curve, 0.76; 95% confidence interval [CI], 0.57-0.95, p = 0.02). Serum Gd-IgA1 level was an independent factor for recurrent IgAN (odds ratio, 17.60; 95% CI, 1.33-233.03, p = 0.03). There was no significant difference in graft or patient survival between the two groups. CONCLUSION Serum Gd-IgA1 can be used as a diagnostic biomarker for recurrent IgAN in KT.
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Affiliation(s)
- Woo Yeong Park
- Division of Nephrology, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Republic of Korea.,Keimyung University Kidney Institute, Daegu, Republic of Korea.,Institute for Cancer Research, Keimyung University, Daegu, Republic of Korea
| | - Yaerim Kim
- Division of Nephrology, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Republic of Korea.,Keimyung University Kidney Institute, Daegu, Republic of Korea
| | - Jin Hyuk Paek
- Division of Nephrology, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Republic of Korea.,Keimyung University Kidney Institute, Daegu, Republic of Korea
| | - Kyubok Jin
- Division of Nephrology, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Republic of Korea.,Keimyung University Kidney Institute, Daegu, Republic of Korea
| | - Seungyeup Han
- Division of Nephrology, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Republic of Korea.,Keimyung University Kidney Institute, Daegu, Republic of Korea
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Metter C, Torrealba JR. Pathology of the kidney allograft. Semin Diagn Pathol 2020; 37:148-153. [PMID: 32249077 DOI: 10.1053/j.semdp.2020.03.005] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Revised: 03/23/2020] [Accepted: 03/24/2020] [Indexed: 11/11/2022]
Abstract
The kidney biopsy still represents the best approach to diagnose renal transplant complications. It is considered the gold standard in the diagnosis of rejection and non-rejection complications. Although invasive, it is a safe procedure with a very low complication rate. With adequate sampling, changes related to antibody-mediated rejection (ABMR) and T-cell mediated rejection (TCMR) can be identified. However, the pathologist needs to be aware of the many other complications, not related to rejection, that can affect the allograft function. Examples include viral infections, drug toxicity, systemic diseases such as hypertension and diabetes, and recurrent or de novo glomerulopathy, among others. In this article, we review the recent classification of pathology of the kidney allograft, with reference to recent consensus reached at the most recent Banff renal allograft classification meetings, and also highlight common non-rejection complications of the kidney transplant.
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Affiliation(s)
- Christopher Metter
- Department of Pathology, University of Texas Southwestern Medical Center, Professional Office Building I, 3rd Floor Suite HP3.370, Room HP3.392 ,5959 Harry Hines Blvd, Dallas, TX 75390, TX, United States
| | - Jose R Torrealba
- Department of Pathology, University of Texas Southwestern Medical Center, Professional Office Building I, 3rd Floor Suite HP3.370, Room HP3.392 ,5959 Harry Hines Blvd, Dallas, TX 75390, TX, United States.
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Tefik T, Ciftci HŞ, Karadeniz MS, Yazici H, Oktar T, Kocak T, Ziylan O, Turkmen A, Oğuz FS, Nane I. Predictive Value of Interleukin 2 and Interleukin 8 on Early Rejection in Living Related Kidney Transplant Recipients. Transplant Proc 2019; 51:1078-1081. [PMID: 31101174 DOI: 10.1016/j.transproceed.2019.02.015] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Revised: 02/20/2019] [Accepted: 02/20/2019] [Indexed: 01/14/2023]
Abstract
INTRODUCTION Early diagnosis of rejection in kidney transplant (KTx) recipients is of paramount importance for long-term graft survival. Cytokines play an important role in rejection via activating T cells. Neutrophil accumulation in the graft indicates cell-mediated rejection. Cellular infiltration is mediated through chemoattractant factors. The aim of this study was to investigate the relationship between graft function and serum levels of interleukin 2 (IL-2) and interleukin 8 (IL-8) in KTx. METHOD Sixty-five patients undergoing KTx were enrolled in the study. Serum samples of IL-2 and IL-8 were collected the day before the operation, on postoperative days 1 and 7 day, and during the first and third month after the onset of rejection. The enzyme-linked immunosorbent assay method was used to determine the IL-2 and IL-8 values. RESULTS A total of 9 (13.8%) patients had rejection documented on biopsy samples. Fifty-six patients had stable graft function (SGF). IL-2 and IL-8 values before KTx of both the rejected and SGF patients were not statistically different. Univariate analysis revealed that IL-2 and IL-8 were correlated with rejection (P = .046, P = .015). IL-8 levels were higher in the rejection group compared to the SGF group on the seventh day and first month postoperatively (P = .023, P = .038). The rejection group maintained higher levels of IL-8 for 11 days (range: 7-30) compared to the SGF group (P = .002) and the IL-8 levels correlated with serum creatinine levels (r = 0.621, P = .001). IL-2 levels were higher in the rejection group on days 1 and 7 compared to the SGF group (P = .042, P = .031). IL-2 and IL-8 levels were correlated with low eGFR in the third month in the rejection group (r = 0.421, P = .037; r = 0.518, P = .008). CONCLUSION Determining the cytokine levels in the early post-KTx period may be helpful in tailoring immunosuppressive regimens in patients with a risk of rejection.
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Affiliation(s)
- T Tefik
- Department of Urology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
| | - H Ş Ciftci
- Department of Medical Biology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - M S Karadeniz
- Department of Anesthesia, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - H Yazici
- Division of Nephrology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - T Oktar
- Department of Urology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - T Kocak
- Department of Urology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - O Ziylan
- Department of Urology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - A Turkmen
- Division of Nephrology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - F S Oğuz
- Department of Medical Biology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - I Nane
- Department of Urology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
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Beniwal P, Gaur N, Malhotra V, Agrawal D, Singh S, Sharma S, Jhorawat R, Joshi P, Khandelwal S, Gupta V. Significance and safety of renal allograft biopsies: Experience from a tertiary care center in India. INDIAN JOURNAL OF TRANSPLANTATION 2019. [DOI: 10.4103/ijot.ijot_10_19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Diagnostic efficacy and safety of ultrasound-guided kidney transplant biopsy using cortex-only view: a retrospective single-center study. Eur Radiol 2018; 29:5272-5279. [PMID: 30560360 DOI: 10.1007/s00330-018-5910-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2018] [Revised: 10/24/2018] [Accepted: 11/22/2018] [Indexed: 01/08/2023]
Abstract
PURPOSE Cortical biopsy is the cornerstone to reveal a cause of unexplained dysfunction of the kidney transplant. Nevertheless, only a few studies have reported the biopsy technique with its performance. We described a novel technique of ultrasound (US)-guided kidney transplant biopsy using cortex-only view and analyzed its diagnostic efficacy and safety. MATERIALS AND METHODS Between January 2014 and December 2016, a consecutive series of 188 patients who underwent US-guided kidney transplant biopsy using cortex-only view by an experienced radiologist were evaluated (mean age, 46.1 ± 12.5 years; range, 21-79 years). Biopsy time, biopsy distance, biopsy core number, and glomerular number per patient were recorded. Successful biopsy (e.g., adequate, 10 or more glomeruli; marginal, 7-9 glomeruli) and complication rates were investigated, using Banff criteria and Clavien-Dindo classification, respectively. RESULTS Mean biopsy time, distance, and core number were 20.6 ± 6.7 min (range, 10-44 min), 3.2 ± 0.7 cm (range, 2.1-5.4 cm), and 1.9 ± 0.3 (range, 1.0-3.0), respectively. Mean glomerular number per patient was 20.4 ± 10.0 (range, 0-54). Adequate and marginal biopsy rates were 87.2% (164/188) and 95.2% (179/188), respectively. There was no major complication requiring treatment (no patient with Clavien-Dindo grade 2 or greater complication), while there were self-limiting minor complications in 5 patients (overall complication rate, 2.7%). CONCLUSION US-guided biopsy using cortex-only view is feasible and safe in sampling cortical tissues of kidney transplant. KEY POINTS • Ultrasound (US)-guided kidney transplant biopsy using cortex-only view is feasible and safe. • Adequate and marginal biopsy rates were 87.2% and 95.2%, respectively. • No major complication requiring treatment occurred after biopsy.
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Saygılı ES, Seyahi N, Durak H, Soylu H, Cengiz M, Altıparmak MR. Greft sağkalımını etkileyen faktörlerin transplant böbrek biyopsileriyle değerlendirilmesi. DICLE MEDICAL JOURNAL 2018. [DOI: 10.5798/dicletip.457229] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
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Deger E, Celik A, Dheir H, Turunc V, Yardimci A, Torun M, Cihangiroglu M. Rejection evaluation after renal transplantation using MR diffusion tensor imaging. Acta Radiol 2018; 59:876-883. [PMID: 28975804 DOI: 10.1177/0284185117733777] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Background Renal allograft dysfunction monitoring is mainly performed using the serum creatinine (SC) level, Doppler ultrasound (US), or renal biopsy. Recently proposed diffusion-based magnetic resonance imaging (MRI) methods have been explored as new, non-invasive tools for assessing renal function after transplantation. Purpose To investigate the value of fractional anisotropy (FA) measurements in the evaluation of acute rejection cases after renal transplant. Material and Methods Doppler US and MRI diffusion tensor imaging (DTI) were performed in 21 patients with graft dysfunction requiring graft biopsy after renal transplantation and in 21 patients with normal graft function. The MR examinations were performed on a 1.5-T MRI using two b-values (0 and 800 s/mm2). FA values were measured from the cortex and medulla of the transplanted kidney at the upper, middle, and lower poles. Results Twenty-one transplant patients diagnosed with acute rejection (Group 1) were compared to the control group of 21 transplant patients with normal graft function (Group 2). The measured FA values of the medulla were 0.19 ± 0.02 and 0.22 ± 0.05 ( P = 0.017) for Groups 1 and 2, respectively. On the other hand, the measured FA values of the renal cortex were 0.18 ± 0.04 and 0.18 ± 0.04 ( P = 0.97) for Groups 1 and 2, respectively. Conclusion The good correlation between the renal medulla FA values and allograft function shows that MR DTI has potential for non-invasive functional assessment of transplanted kidneys. On the other hand, the renal cortex FA values had no correlation with the allograft function.
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Affiliation(s)
- Emin Deger
- Department of Radiology, Medicalpark Goztepe Hospital, Istanbul, Turkey
| | - Azim Celik
- GE Healthcare Istanbul, Istanbul, Turkey
| | - Hamad Dheir
- Department of Organ Transplantation, Medicalpark Goztepe Hospital, Istanbul, Turkey
| | - Volkan Turunc
- Department of Organ Transplantation, Medicalpark Goztepe Hospital, Istanbul, Turkey
| | - Ahmet Yardimci
- Department of Biostatistics and Medical Informatics, Akdeniz University Faculty of Medicine, Antalya, Turkey
| | - Mert Torun
- Bahcesehir University Medical School, Istanbul, Turkey
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Senturk Ciftci H, Demir E, Savran Karadeniz M, Tefik T, Yazici H, Nane I, Savran Oguz F, Aydin F, Turkmen A. Serum and Urinary Levels of Tumor Necrosis Factor-Alpha in Renal Transplant Patients. EXP CLIN TRANSPLANT 2017; 16:671-675. [PMID: 29251577 DOI: 10.6002/ect.2017.0166] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
OBJECTIVES Allograft rejection is an important cause of early and long-term graft loss in kidney transplant recipients. Tumor necrosis factor-alpha promotes T-cell activation, the key reaction leading to allograft rejection. Here, we investigated whether serum and urinary tumor necrosis factor-alpha levels can predict allograft rejection. MATERIALS AND METHODS This study included 65 living related-donor renal transplant recipients with mean follow-up of 26 ± 9 months. Serum and urinary tumor necrosis factor-alpha levels were measured at pretransplant and at posttransplant time points (days 1 and 7 and months 3 and 6); serum creatinine levels were also monitored during posttransplant follow-up. Standard enzyme-linked immunoabsorbent assay was used to detect tumor necrosis factor-alpha levels. Clinical variables were monitored. RESULTS Nine of 65 patients (13.8%) had biopsy-proven rejection during follow-up. Preoperative serum and urinary tumor necrosis factor-alpha levels were not significantly different when we compared patients with and without rejection. Serum tumor necrosis factor-alpha levels (in pg/mL) were significantly higher in the allograft rejection versus nonrejection group at day 7 (11.5 ± 4.7 vs 15.4 ± 5.8; P = .029) and month 1 (11.1 ± 4.8 vs 17.8 ± 10.9; P =.003). Urinary tumor necrosis factor-alpha levels (in pg/mL) were also elevated in the allograft rejection versus the nonrejection group at days 1 (10.2 ± 2.5 vs 14.1 ± 6.8; P = .002) and 7 (9.8 ± 2.2 vs 14.5 ± 2.7; P < .001) and at months 1 (8.0 ± 1.7 vs 11.8 ± 2.4; P < .001), 3 (7.7 ± 1.6 vs 9.6 ± 1.7; P = .002), and 6 (7.4 ± 1.6 vs 8.9 ± 0.9; P = .005). CONCLUSIONS Our preliminary findings suggest that tumor necrosis factor-alpha has a role in diagnosing renal transplant rejection. Serum and urinary tumor necrosis factor-alpha levels may be a possible predictor for allograft rejection.
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Affiliation(s)
- Hayriye Senturk Ciftci
- From the Department of Medical Biology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
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Oates A, Ahuja S, Lee MM, Phelps AS, Mackenzie JD, Courtier JL. Pediatric renal transplant biopsy with ultrasound guidance: the 'core' essentials. Pediatr Radiol 2017; 47:1572-1579. [PMID: 28573315 DOI: 10.1007/s00247-017-3905-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2017] [Revised: 04/03/2017] [Accepted: 05/11/2017] [Indexed: 12/16/2022]
Abstract
This review provides a comprehensive and practical approach to pediatric percutaneous renal transplant biopsies, highlighting techniques and strategies to optimize adequate sample yield and ensure patient safety. In children with end-stage renal disease, transplantation is the preferred choice of therapy, providing for overall lower long-term morbidity and mortality compared with dialysis. In the ongoing management of renal transplant patients, core tissue sampling via a percutaneous renal biopsy remains the gold standard when transplant dysfunction is suspected. Indications for renal transplant biopsy and techniques/tools for adequate sample yield are discussed. Strategies for common challenges such as poor visualization and renal transplant mobility are addressed. We discuss the clinical signs, techniques and imaging findings for common complications including hematomas, arteriovenous fistulas and pseudoaneurysms. Although the percutaneous renal transplant biopsy procedure is generally safe with rare complications, care must be taken to ensure major complications are promptly recognized and treated. Adequate tissue samples obtained via renal biopsy are imperative to promptly identify transplant rejection to provide valuable information for patient diagnosis, treatment and outcomes. Radiologist and nephrologist attention to proper ultrasound techniques and optimal biopsy tools are critical to ensure tissue adequacy and minimize complications.
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Affiliation(s)
- Aris Oates
- Division of Nephrology, Department of Pediatrics, University of California, 550 16th St., 5th floor, Mailstop 3214, San Francisco, CA, 94143- 3214, USA.
| | - Saveen Ahuja
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
| | - Marsha M Lee
- Division of Nephrology, Department of Pediatrics, University of California, 550 16th St., 5th floor, Mailstop 3214, San Francisco, CA, 94143- 3214, USA
| | - Andrew S Phelps
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
| | - John D Mackenzie
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
| | - Jesse L Courtier
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
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Canpolat T, Ozdemir BH, Torun D, Caliskan K, Haberal M. Four-Year Analyses of Renal Graft Biopsies: A Single-Center Pathology Experience. EXP CLIN TRANSPLANT 2016; 15:171-178. [PMID: 27099951 DOI: 10.6002/ect.2015.0264] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Kidney transplant is the best treatment for patients with end-stage renal disease. Long-term graft survival depends on the protection of renal allograft function. Renal allograft biopsy is the most important method for examining an allograft function. Biopsy provides critical information, enabling diagnosis and grading of pathologic changes, prediction of response to therapy, and long-term graft prognosis. MATERIALS AND METHODS We reviewed the medical records of patients who underwent renal transplant from living and deceased donors at Baskent University Adana Teaching and Research Hospital between 2010 and 2014 and who had an indication for biopsy. Clinical characteristics and laboratory results of patients were recorded. Patient biopsy samples were examined according to the Banff 2009 classification. RESULTS Between 2010 and 2014, there were 175 renal transplants performed at our hospital, with 134 recipients (76.6%) having living-donor and 41 recipients (23.4%) having deceased-donor transplants. Fifty-one patients (29.1%) were children, and 124 patients (70.9%) were adults. We found that there were 123 biopsies made from 75 transplant patients over a 4-year period. When examined according to Banff 2009 criteria, the biopsy samples revealed acute T-cell-mediated rejection alone in 14.1% of the samples, acute antibody-mediated rejection in 4%, and a combination of the 2 rejections in 5.7%. Specific infections were detected in 12 patients. The graft nephrectomy rate was 5.1%. CONCLUSIONS This study investigated biopsy results, their relation with patient clinical status and 4-year survival rates, and our pathology experience and found that rejection and infection rates were similar to the literature. Our future studies with a longer follow-up and a larger sample size will likely provide more accurate information about graft survival and biopsy results.
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Affiliation(s)
- Tuba Canpolat
- Department of Pathology, Baskent University School of Medicine, Yuregir, Adana, Turkey
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14
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Sindhi R, Ashokkumar C, Higgs BW, Levy S, Soltys K, Bond G, Mazariegos G, Ranganathan S, Zeevi A. Profile of the Pleximmune blood test for transplant rejection risk prediction. Expert Rev Mol Diagn 2016; 16:387-93. [PMID: 26760313 PMCID: PMC4965161 DOI: 10.1586/14737159.2016.1139455] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
The Pleximmune™ test (Plexision Inc., Pittsburgh, PA, USA) is the first cell-based test approved by the US FDA, which predicts acute cellular rejection in children with liver- or intestine transplantation. The test addresses an unmet need to improve management of immunosuppression, which incurs greater risks of opportunistic infections and Epstein-Barr virus-induced malignancy during childhood. High-dose immunosuppression and recurrent rejection after intestine transplantation also result in a 5-year graft loss rate of up to 50%. Such outcomes seem increasingly unacceptable because children can experience rejection-free survival with reduced immunosuppression. Pleximmune test sensitivity and specificity for predicting acute cellular rejection is 84% and 80% respectively in training set-validation set testing of 214 children. Among existing gold standards, the biopsy detects but cannot predict rejection. Anti-donor antibodies, which presage antibody-mediated injury, reflect late-stage allosensitization as a downstream effect of engagement between recipient and donor cells. Therefore, durable graft and patient outcomes also require accurate management of cellular immune responses in clinical practice.
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Affiliation(s)
- Rakesh Sindhi
- Thomas E. Starzl Transplantation Institute, Hillman Center for Pediatric Transplantation, Children’s Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Department of Transplant Surgery, 4401 Penn Avenue, FP-6/Transplant, Pittsburgh, PA 15224
| | - Chethan Ashokkumar
- Thomas E. Starzl Transplantation Institute, Hillman Center for Pediatric Transplantation, Children’s Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Department of Transplant Surgery, 4401 Penn Avenue, FP-6/Transplant, Pittsburgh, PA 15224
| | - Brandon W Higgs
- Thomas E. Starzl Transplantation Institute, Hillman Center for Pediatric Transplantation, Children’s Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Department of Transplant Surgery, 4401 Penn Avenue, FP-6/Transplant, Pittsburgh, PA 15224
| | - Samantha Levy
- Plexision Inc., 4424 Penn Avenue, Pittsburgh, PA 15224
| | - Kyle Soltys
- Thomas E. Starzl Transplantation Institute, Hillman Center for Pediatric Transplantation, Children’s Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Department of Transplant Surgery, 4401 Penn Avenue, FP-6/Transplant, Pittsburgh, PA 15224
| | - Geoffrey Bond
- Thomas E. Starzl Transplantation Institute, Hillman Center for Pediatric Transplantation, Children’s Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Department of Transplant Surgery, 4401 Penn Avenue, FP-6/Transplant, Pittsburgh, PA 15224
| | - George Mazariegos
- Thomas E. Starzl Transplantation Institute, Hillman Center for Pediatric Transplantation, Children’s Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Department of Transplant Surgery, 4401 Penn Avenue, FP-6/Transplant, Pittsburgh, PA 15224
| | - Sarangarajan Ranganathan
- Tissue Typing Laboratory, Department of Pathology, Children’s Hospital of Pittsburgh of UPMC, 4401 Penn Avenue, Pittsburgh, PA 15224
| | - Adriana Zeevi
- Tissue Typing Laboratory, Department of Pathology, Children’s Hospital of Pittsburgh of UPMC, 4401 Penn Avenue, Pittsburgh, PA 15224
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15
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Redfield RR, McCune KR, Rao A, Sadowski E, Hanson M, Kolterman AJ, Robbins J, Guite K, Mohamed M, Parajuli S, Mandelbrot DA, Astor BC, Djamali A. Nature, timing, and severity of complications from ultrasound-guided percutaneous renal transplant biopsy. Transpl Int 2016; 29:167-172. [PMID: 26284692 DOI: 10.1111/tri.12660] [Citation(s) in RCA: 69] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 05/29/2015] [Accepted: 07/23/2015] [Indexed: 02/06/2023]
Abstract
We sought to review our kidney transplant biopsy experience to assess the incidence, type, presenting symptoms, and timing of renal transplant biopsy complications, as well as determine any modifiable risk factors for postbiopsy complications. This is an observational analysis of patients at the University of Wisconsin between January 1, 2000, and December 31, 2009. Patients with an INR ≥1.5 or platelet counts less than 50 000 were not biopsied. An 18-gauge needle was used for biopsy. Over the study period, 3738 biopsies were performed with 66 complications (1.8%). No deaths occurred. A total of 0.7% were mild complications, 0.7% were moderate complications, 0.21% were severe complications, and 0.19% were life-threatening. Most complications occurred within the 4-h postbiopsy period, although serious complications were often delayed: 67% of complications requiring surgical intervention presented greater than 4 h after biopsy. Biopsy within 1 week of transplant had a 311% increased risk of a complication. Postbiopsy reduction in hematocrit and hemoglobin at 4 h was associated with a complication. In conclusion, life-threatening complications after renal allograft biopsy occurred in 0.19% of patients. Most complications occurred within 4 h postprocedure; however, many serious complications occurred with a time delay after initially uneventful monitoring. The only clinically significant laboratory predictor of a complication was a fall in the hematocrit or hemoglobin within 4 h. Patients biopsied within a week of transplant were at the highest risk for a complication and should therefore be most closely monitored.
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Affiliation(s)
- Robert R Redfield
- Division of Transplant Surgery, University of Wisconsin Hospital and Clinics, Madison, WI, USA
| | - Kasi R McCune
- Division of Transplant Surgery, University of Wisconsin Hospital and Clinics, Madison, WI, USA
| | - Avinash Rao
- Division of Transplant Surgery, University of Wisconsin Hospital and Clinics, Madison, WI, USA
| | - Elizabeth Sadowski
- Department of Radiology, University of Wisconsin Hospital and Clinics, Madison, WI, USA
| | - Meghan Hanson
- Department of Radiology, University of Wisconsin Hospital and Clinics, Madison, WI, USA
| | - Amanda J Kolterman
- Department of Radiology, University of Wisconsin Hospital and Clinics, Madison, WI, USA
| | - Jessica Robbins
- Department of Radiology, University of Wisconsin Hospital and Clinics, Madison, WI, USA
| | - Kristie Guite
- Department of Radiology, University of Wisconsin Hospital and Clinics, Madison, WI, USA
| | - Maha Mohamed
- Division of Nephrology, Department of Medicine, University of Wisconsin Hospital and Clinics, Madison, WI, USA
| | - Sandesh Parajuli
- Division of Nephrology, Department of Medicine, University of Wisconsin Hospital and Clinics, Madison, WI, USA
| | - Didier A Mandelbrot
- Division of Nephrology, Department of Medicine, University of Wisconsin Hospital and Clinics, Madison, WI, USA
| | - Brad C Astor
- Department of Medicine and Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Arjang Djamali
- Division of Nephrology, Department of Medicine, University of Wisconsin Hospital and Clinics, Madison, WI, USA
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16
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Kari JA, Ma AL, Dufek S, Mohamed I, Mamode N, Sebire NJ, Marks SD. Can pre-implantation biopsies predict renal allograft function in pediatric renal transplant recipients? Saudi Med J 2015; 36:1299-304. [PMID: 26593162 PMCID: PMC4673366 DOI: 10.15537/smj.2015.11.12976] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Objectives: To determine the utility of pre-implantation renal biopsy (PIB) to predict renal allograft outcomes. Methods: This is a retrospective review of all patients that underwent PIB from January 2003 to December 2011 at the Great Ormond Street Hospital for Children in London, United Kingdom. Thirty-two male patients (56%) aged 1.5-16 years (median: 10.2) at the time of transplantation were included in the study and followed-up for 33 (6-78) months. The results were compared with 33 controls. Results: The PIB showed normal histopathological findings in 13 patients (41%), mild chronic vascular changes in 8 (25%), focal tubular atrophy in one, moderate to severe chronic vascular change in 3, mild to moderate acute tubular damage in 6, and tissue was inadequate in one subject. Delayed graft function (DGF) was observed in 3 patients; 2 with vascular changes in PIB, and one with normal histopathological findings. Two subjects with PIB changes lost their grafts. The estimated glomerular filtration rate at 3-, and 6-months post-transplantation was lower in children with abnormal PIB changes compared with those with normal PIB. There was one case of DGF in the control group, and 4 children lost their grafts including the one with DGF. Conclusion: Pre-implantation renal biopsy can provide important baseline information of the graft with implications on subsequent medical treatment for pediatric renal transplant recipients.
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Affiliation(s)
- Jameela A Kari
- Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia. E-mail.
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17
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Medullary nephritis in the diagnosis of acute cellular rejection. Pathol Res Pract 2015; 211:811-5. [DOI: 10.1016/j.prp.2015.07.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2014] [Revised: 05/30/2015] [Accepted: 07/13/2015] [Indexed: 11/24/2022]
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18
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Zapf A, Gwinner W, Karch A, Metzger J, Haller H, Koch A. Non-invasive diagnosis of acute rejection in renal transplant patients using mass spectrometry of urine samples - a multicentre phase 3 diagnostic accuracy study. BMC Nephrol 2015; 16:153. [PMID: 26374548 PMCID: PMC4570292 DOI: 10.1186/s12882-015-0146-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Accepted: 08/29/2015] [Indexed: 12/20/2022] Open
Abstract
Background Reliable and timely detection of acute rejection in renal transplant patients is important to preserve the allograft function and to prevent premature allograft failure. The current gold standard for the rejection diagnosis is an allograft biopsy which is usually performed upon an unexplained decline in allograft function. Because of the invasiveness of the biopsy, non-invasive tests have been suggested to diagnose acute rejection including mass spectrometry analysis of urine samples. Design and methods The aim of this study is to examine the diagnostic accuracy of mass spectrometry analysis in urine for the diagnosis of acute rejections using the biopsy as gold-standard. The study is an ongoing prospective, single-arm, multicentre, phase 3 diagnostic accuracy study. It started in October 2011 and will be concluded in December 2015. Patient within the first year after transplantation who are scheduled for a biopsy to clarify unexplained impairment of the allograft are consecutively recruited into the study. The overall sample size (n = 600) was calculated to demonstrate a sensitivity of 83 % and a specificity of 70 % for a one-sided type one error of 2.5 % and a power of 80 % per hypothesis. Biopsy evaluation and mass spectrometry analysis of urine samples (obtained immediately before biopsy) are performed independently by different readers without knowledge from the respective other assessment. The follow-up observation period is 6 months. For the primary analysis, the lower limits of the two-sided 95 % Wald confidence intervals for sensitivity and specificity will be compared with the pre-specified thresholds (83 % for sensitivity and 70 % for specificity). In secondary analyses the predictive values, the diagnostic measures in subgroups, and the clinical course will be assessed. Discussion Previous phase 2 diagnostic accuracy studies (in small selected study populations) provided sufficient evidence to suggest mass spectrometry on urine samples as a promising approach to detect acute rejections. This study determines the diagnostic performance of the test in the routine setting of post-transplant patient care, compared to the biopsy-based rejection diagnosis. The next step would be a randomized trial to compare the two diagnostic strategies (including the urine test or not) in relation to patient relevant endpoints. Trial registration NCT01315067; March 14, 2011 Electronic supplementary material The online version of this article (doi:10.1186/s12882-015-0146-x) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Antonia Zapf
- Institute for Medical Statistics, University Medical Center Göttingen, Humboldtallee 32, 37073, Göttingen, Germany.
| | - Wilfried Gwinner
- Department of Nephrology, Medical School Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
| | - Annika Karch
- Institute for Biostatistics, Medical School Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
| | - Jochen Metzger
- Mosaiques Diagnostics and Therapeutics, Rotenburger Str. 20, 30659, Hannover, Germany.
| | - Hermann Haller
- Department of Nephrology, Medical School Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
| | - Armin Koch
- Institute for Biostatistics, Medical School Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
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19
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Broecker V, Mengel M. The significance of histological diagnosis in renal allograft biopsies in 2014. Transpl Int 2014; 28:136-43. [PMID: 25205033 DOI: 10.1111/tri.12446] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2014] [Revised: 06/26/2014] [Accepted: 09/01/2014] [Indexed: 01/20/2023]
Abstract
In 2014, the renal allograft biopsy still represents the best available diagnostic 'gold' standard to assess reasons for allograft dysfunction. However, it is well recognized that histological lesion observed in the biopsy is of limited diagnostic specificity and that the Banff classification as the international diagnostic standard represents mere expert consensus. Here, we review the role of the renal allograft biopsy in different clinical and diagnostic settings. To increase diagnostic accuracy and to compensate for lack of specificity, the interpretation of biopsy pathology needs to be within the clinical context, primarily defined by time post-transplantation and patient-specific risk profile. With this in mind, similar histopathological patterns will lead to different conclusions with regard to diagnosis, disease grading and staging and thus to patient-specific clinical decision-making. Consensus generation for such integrated diagnostic approach, preferably including new molecular tools, represents the next challenge to the transplant community on its way to precision medicine in transplantation.
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Affiliation(s)
- Verena Broecker
- Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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20
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Bhat ZY, Bostwick DG, Hossain D, Zeng X. Participation of functionally active plasma cells in acute rejection and response to therapy in renal allografts. DNA Cell Biol 2014; 33:448-54. [PMID: 24684655 DOI: 10.1089/dna.2014.2371] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Acute rejection (AR) includes T-cell-mediated and antibody-mediated rejection. The inflammatory infiltrate comprised not only T cells but also varying amounts of B cells (CD20(+)) and plasma cells (CD138(+)). The latter are associated with poor clinical outcomes, but their functional status is not clear. The phosphorylation of the S6 ribosomal protein (p-S6RP) is present in cells that are metabolically active, thus identifying functionally active antibody-secreting plasma cells. This study was designed to evaluate the clinical significance of functionally active p-S6RP plasma cells in AR in renal allografts. Renal allografts with biopsy evidence of AR during 2006-2009 were included. Immunohistochemistry staining for CD20, CD138, and p-S6RP was performed on paraffin-embedded slides and scaled as 0-6. The response to antirejection treatment was assessed by the serum creatinine ratio (CrR) at rejection episode (time 0) and following treatment (4 and 12 weeks). Patients with lower scores (0-2) were compared with a higher scored group (3-6). The T-test was conducted using statistical significance of p<0.05. A total of 28 patients (40.7 ± 14.3 year; M:F=15:13) were diagnosed with acute T-cell-mediated rejection (I and II). The p-S6RP staining in the high-score group had a significantly higher CrR (p<0.05) than the low-score group at the time of biopsy, 4 and 12 weeks following treatment. There was no significant difference in the CrR between groups for CD20 or CD138 staining. Functional antibody-secreting p-S6RP plasma cells are actively participating in AR and associated with poor response to treatment in renal allografts.
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Affiliation(s)
- Zeenat Yousuf Bhat
- 1 Division of Nephrology, Department of Internal Medicine, Wayne State University , Detroit, Michigan
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21
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Matignon M, Ding R, Dadhania DM, Mueller FB, Hartono C, Snopkowski C, Li C, Lee JR, Sjoberg D, Seshan SV, Sharma VK, Yang H, Nour B, Vickers AJ, Suthanthiran M, Muthukumar T. Urinary cell mRNA profiles and differential diagnosis of acute kidney graft dysfunction. J Am Soc Nephrol 2014; 25:1586-97. [PMID: 24610929 DOI: 10.1681/asn.2013080900] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Abstract
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.
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Affiliation(s)
- Marie Matignon
- Division of Nephrology and Hypertension, Department of Medicine and Assistance Publique-Hôpitaux de Paris, Groupe Henri Mondor-Albert Chenevier, Nephrology and Transplantation Department, Centre d'Investigation Clinique-BioThérapies 504 and Institut National de la Santé et de la Recherche Médicale U955 and Paris XII University, Créteil, France
| | - Ruchuang Ding
- Division of Nephrology and Hypertension, Department of Medicine and
| | - Darshana M Dadhania
- Division of Nephrology and Hypertension, Department of Medicine and Departments of Transplantation Medicine and
| | - Franco B Mueller
- Division of Nephrology and Hypertension, Department of Medicine and
| | - Choli Hartono
- Division of Nephrology and Hypertension, Department of Medicine and Departments of Transplantation Medicine and
| | | | - Carol Li
- Division of Nephrology and Hypertension, Department of Medicine and
| | - John R Lee
- Division of Nephrology and Hypertension, Department of Medicine and Departments of Transplantation Medicine and
| | - Daniel Sjoberg
- Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York; and
| | - Surya V Seshan
- Pathology, New York Presbyterian Hospital-Weill Cornell Medical Center, New York, New York
| | - Vijay K Sharma
- Division of Nephrology and Hypertension, Department of Medicine and
| | - Hua Yang
- Division of Nephrology and Hypertension, Department of Medicine and
| | - Bakr Nour
- Department of Surgery, Weill Cornell Medical College in Qatar, Doha, Qatar
| | - Andrew J Vickers
- Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York; and
| | - Manikkam Suthanthiran
- Division of Nephrology and Hypertension, Department of Medicine and Departments of Transplantation Medicine and
| | - Thangamani Muthukumar
- Division of Nephrology and Hypertension, Department of Medicine and Departments of Transplantation Medicine and
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Maluf DG, Dumur CI, Suh JL, Scian MJ, King AL, Cathro H, Lee JK, Gehrau RC, Brayman KL, Gallon L, Mas VR. The urine microRNA profile may help monitor post-transplant renal graft function. Kidney Int 2014; 85:439-449. [PMID: 24025639 PMCID: PMC3946645 DOI: 10.1038/ki.2013.338] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2012] [Revised: 06/06/2013] [Accepted: 06/20/2013] [Indexed: 02/08/2023]
Abstract
Noninvasive, cost-effective biomarkers that allow accurate monitoring of graft function are needed in kidney transplantation. Since microRNAs (miRNAs) have emerged as promising disease biomarkers, we sought to establish an miRNA signature in urinary cell pellets comparing kidney transplant patients diagnosed with chronic allograft dysfunction (CAD) with interstitial fibrosis and tubular atrophy and those recipients with normal graft function. Overall, we evaluated 191 samples from 125 deceased donor primary kidney transplant recipients in the discovery, initial validation, and the longitudinal validation studies for noninvasive monitoring of graft function. Of 1733 mature miRNAs studied using microarrays, 22 were found to be differentially expressed between groups. Ontology and pathway analyses showed inflammation as the principal biological function associated with these miRNAs. Twelve selected miRNAs were longitudinally evaluated in urine samples of an independent set of 66 patients, at two time points after kidney transplant. A subset of these miRNAs was found to be differentially expressed between groups early after kidney transplant before histological allograft injury was evident. Thus, a panel of urine miRNAs was identified as potential biomarkers for monitoring graft function and anticipating progression to CAD in kidney transplant patients.
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Affiliation(s)
- Daniel G Maluf
- University of Virginia, Department of Surgery, PO Box 800679, Charlottesville, VA 22908-0679
| | - Catherine I Dumur
- Virginia Commonwealth University, Department of Pathology, PO Box 980662, VA 23298-0662
| | - Jihee L Suh
- University of Virginia, Department of Surgery, PO Box 800679, Charlottesville, VA 22908-0679
| | - Mariano J Scian
- University of Virginia, Department of Surgery, PO Box 800679, Charlottesville, VA 22908-0679
| | - Anne L King
- Virginia Commonwealth University, Division of Transplant, PO Box 980645, VA 23219-0645
| | - Helen Cathro
- Virginia Commonwealth University, Department of Pathology, PO Box 980662, VA 23298-0662
| | - Jae K Lee
- University of Virginia, Division of Biostatistics, Department of Public Health Sciences, PO Box 800717, VA 22908-0717
| | - Ricardo C Gehrau
- University of Virginia, Department of Surgery, PO Box 800679, Charlottesville, VA 22908-0679
| | - Kenneth L Brayman
- University of Virginia, Department of Surgery, PO Box 800679, Charlottesville, VA 22908-0679
| | - Lorenzo Gallon
- Northwestern University, Division of Nephrology, Department of Internal Medicine, Comprehensive Transplant Center, Chicago, IL 60611
| | - Valeria R Mas
- University of Virginia, Department of Surgery, PO Box 800679, Charlottesville, VA 22908-0679
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23
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Xie L, Ichimaru N, Morita M, Chen J, Zhu P, Wang J, Urbanellis P, Shalev I, Nagao S, Sugioka A, Zhong L, Nonomura N, Takahara S, Levy GA, Li XK. Identification of a novel biomarker gene set with sensitivity and specificity for distinguishing between allograft rejection and tolerance. Liver Transpl 2012; 18:444-54. [PMID: 22162188 DOI: 10.1002/lt.22480] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Here we examined whether the expression of a novel immunoregulatory gene set could be used to predict outcomes in murine models of rapamycin-induced cardiac tolerance, spontaneous hepatic tolerance, and cardiac rejection. The expression of the immunoregulatory gene set was assessed with the GeXP multiplex reverse-transcription polymerase chain reaction (RT-PCR) analysis system, and it was correlated to the pathological and biochemical parameters of the allografts. In rejecting cardiac grafts, the increased expression of an inflammatory set of genes, which included CD45, CD4, CD25, suppressor of cytokine signaling 2, cytotoxic T lymphocyte-associated protein 4 (CTLA4), selectin lymphocyte, interferon-γ (IFN-γ), programmed cell death 1 (Pdcd1), and granzyme B (Gzmb), was seen 8 days after transplantation along with histological evidence of severe allograft rejection. In tolerant cardiac allografts, the expression of fibrinogen-like protein 2 (Fgl2), Pdcd1, killer cell lectin-like receptor G1 (Klrg1), CTLA4, and lymphocyte-activation gene 3 was associated with tolerance. In a model of liver allograft tolerance, the increased expression of lectin galactose-binding soluble 1, Fgl2, CD39, phosphodiesterase 3B, Klrg1, forkhead box P3 (Foxp3), and transforming growth factor β as well as the inflammatory set of genes was observed 8 to 14 days after transplantation (ie, when there was severe inflammatory injury). At a later time when the liver allografts had been fully accepted and were histologically normal, the expression of the inflammatory set of genes returned to the baseline, but the expression of the tolerogenic set of genes was still increased. Genes that were expressed in tolerant cardiac and liver allografts included Fgl2, Klrg1, and Foxp3, whereas genes associated with rejection included CD25, Gzmb, and IFN-γ. Our data indicate that monitoring the graft expression of a novel biomarker gene set with the GeXP multiplex RT-PCR analysis system may allow differentiation between rejection and tolerance.
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Affiliation(s)
- Lin Xie
- Division of Radiation Safety and Immune Tolerance, National Research Institute for Child Health and Development, Tokyo, Japan
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24
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Abstract
This article describes the current state-of-the-art technique of percutaneous transplant renal biopsy. A brief overview of the history of transplant renal biopsy is given. The indications and contraindications are discussed, including pre- and postprocedure patient management. The technique of the procedure and the devices that are available in the market are described.
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Affiliation(s)
- Iftikhar Ahmad
- Assistant Professor of Radiology, Indiana University School of Medicine, University Hospital, Indianapolis, Indiana
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25
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Waiser J, Schreiber M, Budde K, Böhler T, Kraus W, Hauser I, Riess R, Neumayer HH. Prognostic value of the Banff classification. Transpl Int 2011. [DOI: 10.1111/j.1432-2277.2000.tb01995.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Brown K, Moxham V, Karegli J, Phillips R, Sacks SH, Wong W. Ultra-localization of Foxp3+ T cells within renal allografts shows infiltration of tubules mimicking rejection. THE AMERICAN JOURNAL OF PATHOLOGY 2007; 171:1915-22. [PMID: 17991712 DOI: 10.2353/ajpath.2007.070396] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Kidney transplant recipients are monitored for rejection by measurement of serum creatinine and graft biopsies. Biopsy samples are evaluated according to the Banff classification, which states that infiltration of tubules by mononuclear cells is an indicator of acute rejection. However, regulatory T cells play a crucial role in the overall immune response and are also present within transplanted tissue. We hypothesize that infiltration of mononuclear cells within kidney grafts is not always associated with rejection, especially if a high proportion of this infiltrate is regulatory T cells. Using a life-sustaining mouse kidney transplant model, we found that mononuclear cell tubular infiltration can occur in both rejecting and tolerant grafts. However, tolerant kidney grafts demonstrated a higher and sustained level of Foxp3+ regulatory cells. Importantly, a significant proportion of these cells were found within tubules. In cases in which graft function was normal, these cells were not harmful to the kidney and could be said to be mimicking, rather than causing, rejection.
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Affiliation(s)
- Kathryn Brown
- Department of Nephrology and Transplantation, King's College London School of Medicine at Guy's, King's Hospital, London SE1 9RT, UK
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Mahmoud K, Opelz G, Pelzl S, Daniel V, Sommerer C, Zeier M, Schmidt J, Schönemann C, Schnülle P, Süsal C. Evaluation of hepatocyte growth factor as a sensitive marker for early detection of acute renal allograft rejection. Transplantation 2007; 83:1035-40. [PMID: 17452892 DOI: 10.1097/01.tp.0000259653.41436.24] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND It has been shown that hepatocyte growth factor (HGF), besides its well-established hepatotrophic effect in liver regeneration, is involved in the regeneration of the kidney after injury. In the present study we investigated whether HGF can serve as a marker for detection of acute rejection in the early posttransplantation period. METHODS HGF levels were determined in pre- and posttransplant sera (up to day 21) of 26 recipients with biopsy-proven acute rejection, 30 recipients with acute tubular necrosis (ATN), and 32 recipients without posttransplant complications. RESULTS Although no association was found between pretransplant HGF and death-censored functional graft survival, receiver operating characteristic (ROC) curves demonstrated that HGF measured during the entire posttransplant study period, and especially on days 3 to 5, was a good marker for differentiating recipients who subsequently developed acute rejection from recipients with an uncomplicated course (P<0.0001, specificity 87%, sensitivity 84%). HGF measured from day 3 until day 21 posttransplantation, and especially on days 7 to 9, was also a sensitive marker for differentiating recipients with ATN from recipients with an uncomplicated course (P<0.0001). If considered in combination with sCD30, the diagnostic value of HGF was further improved. While 73% of samples from patients with impending rejection were positive for both HGF and sCD30, 94% of samples from nonrejecting patients were double-negative and none of the samples from this group fell into the double-positive category (P<0.0001). CONCLUSIONS Our data suggest that HGF measured during the early posttransplant period might be a useful parameter for early detection of acute renal allograft rejection.
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Affiliation(s)
- Khaled Mahmoud
- Department of Transplantation Immunology, Institute of Immunology, University of Heidelberg, Heidelberg, Germany
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28
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Silva DM, Garcia JP, Ribeiro AR, Veronese FJ, Edelweiss MI, Gonçalves LF, Manfro RC. Utility of Biopsy in Kidney Transplants With Delayed Graft Function and Acute Dysfunction. Transplant Proc 2007; 39:376-7. [PMID: 17362734 DOI: 10.1016/j.transproceed.2007.01.008] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
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.
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Affiliation(s)
- D M Silva
- Division of Nephrology, Kidney Transplant Program, Hospital de Clínicas de Porto Alegre, UFRGS Medical School, Porto Alegre, RS, Brazil
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29
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Gärtner V, Eigentler TK, Viebahn R. Plasma Cell-Rich Rejection Processes in Renal Transplantation: Morphology and Prognostic Relevance. Transplantation 2006; 81:986-91. [PMID: 16612273 DOI: 10.1097/01.tp.0000215014.40595.ab] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
BACKGROUND Renal transplantation is the most effective therapy in end-stage renal disease. The prognosis of transplant survival is still determined by rejection. Morphologically, this involves interstitial rejection with potential development of vascular rejection (VR) and/or glomerular rejection processes, designated as transplant glomerulopathy (TGP). The cellular infiltrates are usually dominated by lymphocytes and macrophages in differing quantity, characterizing the severity of the rejection processes. METHODS In 14% of the renal transplant biopsies and explants in our investigation (n = 399) plasma cells (PR) predominate in the cellular infiltrate. To determine whether the enrichment of PR has an impact on graft function or could even constitute an independent parameter for transplant survival, we analyzed 109 cases of transplanted patients matched for AR and CR and divided them into those rich and those nonrich in PR. RESULTS In the group rich in PR, PR comprised 30% of all infiltrates in comparison to 5% in the group non-rich in PR. VR and TGP appeared significantly more often in PR-rich rejections (P = 0.0044). The group rich in PR had a significantly more adverse prognosis (P = 0.0024), especially if PR enrichment was observed in the chronic rejection processes (P = 0.0148). In the Cox proportional hazard model the occurrence of VR was the only independent factor. CONCLUSION In itself, plasma-cell enrichment is not a prognostic marker, but it is an indicator of a more adverse outcome because it is often accompanied by the appearance or subsequent development of VR +/- TGP. The detection of PR-rich rejection processes should therefore encourage the clinician to intensify the immunosuppressive schedule.
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30
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Lasmar EP, Lasmar MF, Lasmar LF, Giordano LFC, Lucas F, Borges JM. Progression of the renal graft: treatment of acute rejection based on a biopsy against a presumptive diagnosis. Transplant Proc 2006; 37:2775-6. [PMID: 16182807 DOI: 10.1016/j.transproceed.2005.06.097] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
The aim of this study was to compare the progression of renal grafts following treatment of an acute rejection event based on the histological diagnosis of a graft biopsy compared to a presumptive (clinical and laboratory) diagnosis. A historical cohort was used to study 44 patients undergoing a living haploidentical related donor renal transplant, using a similar immunosuppressive treatment: cyclosporine, azathioprine, and prednisone. Acute rejection events were treated with methylprednisolone (250 mg for 3 to 5 days) based on a histological diagnosis (biopsy group = 14) or on a clinical and laboratory diagnosis (presumptive group = 30), which consisted of an elevation over 20% in plasma creatinine in 24 hours and renal ultrasound or scintigraphy findings. The study demonstrated no significant difference in renal function (plasma creatinine) and other outcomes 2 years following transplantation in both groups. The results show that treatment of acute rejection based on a presumptive diagnosis is not a risk factor for unfavorable outcomes following 2 years of renal transplantation monitoring.
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Affiliation(s)
- E P Lasmar
- Faculdade de Ciências Médicas de Minas Gerais, Hospital Mater Dei, Belo Horizonte, Brazil.
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31
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Hauser IA, Spiegler S, Kiss E, Gauer S, Sichler O, Scheuermann EH, Ackermann H, Pfeilschifter JM, Geiger H, Gröne HJ, Radeke HH. Prediction of Acute Renal Allograft Rejection by Urinary Monokine Induced by IFN-γ (MIG). J Am Soc Nephrol 2005; 16:1849-58. [PMID: 15857922 DOI: 10.1681/asn.2004100836] [Citation(s) in RCA: 88] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
Early diagnosis of acute allograft rejection (AR) is still decisive for long-term renal allograft survival. The aim of this study was to define the role of the chemokine monokine induced by IFN-gamma (MIG) (CXCL9) and IFN-gamma-inducible protein 10 (IP-10) (CXCL10) as early markers of AR in renal transplantation (NTX). In a prospective study, 69 de novo renal transplant recipients were monitored and urine samples were collected after NTX for a median of 29 d. In pH-adjusted urine, MIG and IP-10 were determined by modified ELISA. AR was clinically diagnosed in 15 of 69 recipients and confirmed by biopsy in 14 of 15 AR patients (Banff classification). Corresponding to CXCR3-positive infiltrates in renal tissue, urinary MIG was elevated in 14 of 15 AR patients with a median of 2809 pg/ml (quartile 25% and 75% = 870 and 13,000; n = 15), being significantly (P < 0.0001) different from both nonrejecting allograft patients (NO-AR) (median, 25%, and 75%: 96, 1.0, and 161, n = 54) and healthy controls (median, 25%, and 75%: 144, 19, and 208, n = 13). Urinary MIG predicted AR with a sensitivity of 93% and a specificity of 89%. In AR and NO-AR groups, MIG values correlated well with IP-10 (P < 0.001). MIG values indicated both imminent rejection and response to successful antirejection therapy. MIG was not related to intercurrent infections or other causes for impairment of renal function. In a multivariate analysis, MIG correlated best (P < 0.001) with AR from all AR-associated parameters. In conclusion, urinary MIG serves as a very sensitive and specific predictor for AR, mirrors response to antirejection therapy, and thus may contribute to improved long-term renal allograft survival.
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Affiliation(s)
- Ingeborg A Hauser
- Medical Clinic IV, Department of Nephrology, Clinic of the J.W. Goethe University, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany.
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Jurewicz WA, Miles A. Strategies for ensuring effective surveillance in post-transplant patients: practical organization and clinical evaluation. J Eval Clin Pract 2004; 10:37-56. [PMID: 14731150 DOI: 10.1111/j.1365-2753.2003.00408.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Results of renal transplantation have improved steadily over the years. This article reviews the current status of patient and graft survival and discusses major causes of mortality and renal allograft failure. Review of recent literature demonstrates that the traditional enemies of transplantation, acute rejection and opportunistic infections are no longer major problems facing transplantation. Chronic graft nephropathy and death with functioning graft due to cardiovascular disease are the main challenges in the current era. An impact of an early graft thrombosis, recurrent renal disease and post-transplant malignancies are also reviewed. Chronic graft nephropathy is examined in a context of differences between two calcineurin inhibitors, cyclosporin microemulsion and tacrolimus. Strategies of post-transplant surveillance are suggested.
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Affiliation(s)
- W Adam Jurewicz
- Department of Surgery, University of Wales College of Medicine, Cardiff, UK.
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33
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McCall SJ, Tuttle-Newhall JE, Howell DN, Fields TA. Prognostic significance of microvascular thrombosis in donor kidney allograft biopsies. Transplantation 2003; 75:1847-52. [PMID: 12811244 DOI: 10.1097/01.tp.0000063126.88887.68] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
BACKGROUND With a continuing demand for donor kidneys for organ transplantation, it is important to understand the significance of pathologic findings in the donor organ before transplantation. Microvascular thrombosis is sometimes encountered in association with disseminated intravascular coagulation in the donor, and it is unclear whether this finding may affect immediate allograft function and long-term graft survival. To further elucidate this question, we examined our experience with microvascular thrombosis in donor biopsies in the kidney transplant program at our institution. METHODS Donor kidney biopsies showing microvascular thrombosis were identified from consecutive donor biopsies in the Duke University Medical Center transplant file database between January 1, 1995 and December 31, 2000. These biopsies and all other kidney biopsies and specimens from the recipients of these kidneys thus identified were reviewed. Sections were stained using a variety of methods, including hematoxylin-eosin, periodic acid-Schiff, methenamine silver, and Masson trichrome methods. Clinical records of the transplant recipients of these kidneys were also reviewed to assess allograft performance and survival. RESULTS From 230 consecutive donor kidney biopsies, we identified eight cases exhibiting donor-microvascular thrombosis. Mean follow-up times were 27.5 months for the thrombi group and 35 months for the non-thrombi group. Recipients of grafts with donor thrombi were more likely to exhibit delayed graft function, but graft function at 1 and 2 years and graft survival were similar between the two groups. Subsequent posttransplantation biopsies in five of eight cases showed no evidence of residual thrombosis. CONCLUSIONS These data suggest that the presence of donor microvascular thrombosis does not portend poor outcome in renal transplantation.
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Affiliation(s)
- Shannon J McCall
- Department of Pathology, Duke University Medical Center, Durham, NC, USA
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34
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Pelzl S, Opelz G, Daniel V, Wiesel M, Süsal C. Evaluation of posttransplantation soluble CD30 for diagnosis of acute renal allograft rejection. Transplantation 2003; 75:421-3. [PMID: 12589170 DOI: 10.1097/01.tp.0000044702.18327.66] [Citation(s) in RCA: 78] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
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.
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Affiliation(s)
- Steffen Pelzl
- Department of Transplantation Immunology, Institute of Immunology, University of Heidelberg, Heidelberg, Germany
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35
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Chueh SC, Liao CH, Lai MK. Greater variability of dose-corrected cyclosporine C2 concentrations in renal recipients with acute rejection. Transplant Proc 2003; 35:234-5. [PMID: 12591378 DOI: 10.1016/s0041-1345(02)03984-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Affiliation(s)
- S-C Chueh
- Department of Urology, College of Medicine, National Taiwan University, Taipei, Taiwan.
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36
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Fritsche L, Schlaefer A, Budde K, Schroeter K, Neumayer HH. Recognition of critical situations from time series of laboratory results by case-based reasoning. J Am Med Inform Assoc 2002; 9:520-8. [PMID: 12223504 PMCID: PMC346639 DOI: 10.1197/jamia.m1013] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
OBJECTIVE To develop a technique for recognizing critical situations based on laboratory results in settings in which a normal range cannot be defined, because what is "normal" differs widely from patient to patient. To assess the potential of this approach for kidney transplant recipients, where recognition of acute rejections is based on the pattern of changes in serum creatinine. DESIGN We developed a case-based reasoning algorithm using dynamic time-warping as the measure of similarity which allows comparison of series of infrequent measurements at irregular intervals for retrieval of the most similar historical cases for the assessment of a new situation. MEASUREMENTS The ability to recognize creatinine courses associated with an acute rejection was tested for a set of cases from a database of transplant patient records and compared with the diagnostic performance of experienced physicians. Tests were performed with case bases of various sizes. RESULTS The accuracy of the algorithm increased steadily with the size of the available case base. With the largest case bases, the case-based algorithm reached an accuracy of 78 +/- 2%, which is significantly higher than the performance of experienced physicians (69 +/- 5.3%) (p < 0.001). CONCLUSION The new case-based reasoning algorithm with dynamic time warping as the measure of similarity allows extension of the use of automatic laboratory alerting systems to conditions in which abnormal laboratory results are the norm and critical states can be detected only by recognition of pathological changes over time.
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37
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Fritsche L, Schlaefer A, Budde K, Schroeter K, Neumayer HH. Case-based reasoning algorithm for kidney transplant monitoring. Transplant Proc 2001; 33:3331-3. [PMID: 11750424 DOI: 10.1016/s0041-1345(01)02434-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Affiliation(s)
- L Fritsche
- Department of Nephrology, Charité, Humboldt-University, Berlin, Germany
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38
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Aikawa A, Miyagi M, Hasegawa A, Ohara T, Hadano T, Nakano H, Mori Y, Iwamoto M, Sakai K, Mizuiri S. Glomerular changes in a 1-year posttransplant protocol biopsy as a useful predictive indicator in ABO-incompatible kidney transplantation. Transplant Proc 2000; 32:301-5. [PMID: 10715424 DOI: 10.1016/s0041-1345(99)00964-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Affiliation(s)
- A Aikawa
- Department of Nephrology, Toho University, School of Medicine, Tokyo, Japan.
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Hauet T, Goujon JM, Tallineau C, Carretier M, Eugene M. Early evaluation of renal reperfusion injury after prolonged cold storage using proton nuclear magnetic resonance spectroscopy. Br J Surg 1999; 86:1401-9. [PMID: 10583286 DOI: 10.1046/j.1365-2168.1999.01233.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND Proton nuclear magnetic resonance (NMR) spectroscopy can be used as a non-invasive tool to measure renal damage. In the present investigation, proton NMR spectroscopy of urine was assessed in order to detect cellular damage after different periods of cold ischaemia in two standard preservation solutions. METHODS The isolated perfused pig kidney was used to assess initial renal function after in situ cold flush and cold storage (CS) for 24 or 48 h in two standard preservation solutions: EuroCollins (EC) and University of Wisconsin (UW) solutions. Kidneys flushed with cold heparinized saline and immediately perfused were used as a control group. Kidneys were perfused for 2 h at 37.5 degrees C for functional evaluation. During reperfusion, renal perfusion flow rate was measured. Glomerular filtration rate (GFR), tubular reabsorption of sodium ions, and lactate dehydrogenase (LDH) and N-acetyl-beta-D-glucosaminidase (NAG) excretion were determined. Impairment caused by ischaemia and reperfusion was also determined by histological techniques and proton NMR spectroscopy. RESULTS The perfusion flow rate, GFR and tubular reabsorption of sodium were significantly decreased in experimental groups compared with the control group. There was no significant difference between experimental groups after 24 h of CS. The perfusion flow rate was significantly decreased in the EC group after 48 h of cold ischaemia compared with that in the UW group. After 48 h of CS, GFR and tubular reabsorption of sodium were significantly reduced in the EC group compared with those in the UW group. The release of LDH into the effluent and the urinary excretion of NAG were not significantly different after 24 h of CS. After more than 45 and 60 min of reperfusion respectively, LDH and NAG excretion was no different in the 48-h CS groups. The most relevant resonances determined by proton NMR spectroscopy were of citrate, trimethylamine-N-oxide, lactate, acetate and amino acids. Excretion of these markers was significantly more accurate and efficient to assess renal ischaemia-reperfusion injury than that of biochemical markers. A resonance (P) detected particularly in the EC group after 48 h of CS was identified and correlated well with renal dysfunction. After CS for 48 h and 2 h of reperfusion, renal injury was histologically more pronounced in EC groups than in UW groups. However, the difference was not significant after CS for 24 h. CONCLUSION NMR spectroscopy, which is a non-invasive and non-destructive technique, is more accurate and efficient when assessing kidney damage after cold ischaemia and reperfusion when compared to conventional histological and biochemical analysis.
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Affiliation(s)
- T Hauet
- Laboratoire de Chirurgie Expérimentale-Institut National de Recherche Agronomique, Surgères and EA 2426, Faculté de Médecine and Centre Hospitalier Universitaire Poitiers, France
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40
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Chandraker A. Diagnostic techniques in the work-up of renal allograft dysfunction--an update. Curr Opin Nephrol Hypertens 1999; 8:723-8. [PMID: 10630820 DOI: 10.1097/00041552-199911000-00013] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
After renal transplantation, acute allograft dysfunction secondary to acute rejection occurs in around 30-40% of patients. Although in the majority of patients these episodes are reversible, acute rejection remains a major risk factor for the development of chronic rejection. Remarkably, prior episodes of acute allograft rejection are associated with decreased allograft survival. Histologic examination of the percutaneous core needle transplant biopsy remains the gold standard for the diagnosis of acute rejection. It does, however, have a number of shortcomings, and less invasive procedures that could diagnose incipient rejection and simultaneously provide mechanistic information on the rejection process (allowing delivery of more tailored therapy) are being sought. To address these problems a number of alternative diagnostic procedures have been suggested, including duplex Doppler ultrasound assessment, fine-needle aspiration biopsy, urine cytology, urine cytokine analysis, serum cytokine analysis, and cytokine analysis of biopsy material.
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Affiliation(s)
- A Chandraker
- Renal Division, Laboratory of Immunogenetics and Transplantation, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
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41
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Gaber L, Solez K. Renal allograft pathology: crossing over to the new millennium. Pediatr Transplant 1999; 3:249-51. [PMID: 10562968 DOI: 10.1034/j.1399-3046.1999.00069.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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42
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Dean DE, Kamath S, Peddi VR, Schroeder TJ, First MR, Cavallo T. A blinded retrospective analysis of renal allograft pathology using the Banff schema: implications for clinical management. Transplantation 1999; 68:642-5. [PMID: 10507482 DOI: 10.1097/00007890-199909150-00008] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND We sought to determine whether diagnoses established through the Banff schema for evaluation of renal allograft pathology have implications for clinical management, compared with diagnoses established using descriptive terminology. METHODS All patients included in this study had mild to severe allograft rejection diagnosed, and, as part of a therapeutic protocol, they received OKT3 as primary anti-rejection therapy. We conducted a retrospective review of their renal allograft biopsy specimens and reclassified them, using the Banff schema, without knowledge of clinical information, laboratory data, or previous biopsy interpretation. Although there is no strict correspondence between descriptive diagnostic terminology and the criteria used in the Banff schema, for the purpose of comparisons, the following approximation was used: mild and mild to moderate rejection=Banff borderline and Banff grade 1, moderate and moderate to severe rejection=Banff grades 2A and 2B, and severe rejection=Banff grade 3. The diagnosis was considered concordant when the diagnosis by descriptive terminology and Banff grading were within the adopted approximation. RESULTS Of 96 biopsies specimens with mild to severe allograft rejection, 10 were insufficient for diagnosis, and three had changes of chronic allograft rejection. Of the remaining 83 biopsy specimens, 34 (41%) were concordant in interpretation of rejection grades, whereas 49 (59%) were discrepant. The greatest degree of concordance was in grades 2A (66.7%, 18 of 27) and 2B (64.7% 11 of 17), and the lowest was in the borderline category (11.8%, 2 of 17). The greatest degree of discrepancy was in normal and grade 3 (100%, 3 of 3 and 2 of 2, respectively), and the lowest was in grade 2A (33.3%, 9 of 27). Although primary anti-rejection therapy with OKT3 resulted in a high reversal rate of rejection (98%), there were 5 deaths, 12 graft loses, six episodes of serious infections, and three malignancies in this group of patients during a mean follow-up period of approximately 38 months. CONCLUSIONS Because patients with borderline changes and grades 1 and 2A rejection may be treated differently from patients with higher grades (2B and 3), the use of the Banff schema may allow for better adjustment of immunosuppressive therapy in response to specific grades of acute allograft rejection and may result in decreased complications of immunosuppressive therapy.
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Affiliation(s)
- D E Dean
- Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Ohio 45267-0529, USA
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43
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Khajehdehi P, Junaid SM, Salinas-Madrigal L, Schmitz PG, Bastani B. Percutaneous renal biopsy in the 1990s: safety, value, and implications for early hospital discharge. Am J Kidney Dis 1999; 34:92-7. [PMID: 10401021 DOI: 10.1016/s0272-6386(99)70113-7] [Citation(s) in RCA: 54] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
To determine the parameters associated with significant bleeding and to examine the value of performing a renal biopsy, we studied 83 consecutive patients, including 24 renal allograft recipients, who had undergone percutaneous renal biopsy. The patients were stratified into four groups according to the percentage of decline in their hematocrit (Hct) at 24 hours postbiopsy, as follows: 10% or greater (n = 21; 25%) and less than 10% decline (n = 62; 75%). The latter group was further subgrouped into 5% to 10% (n = 22) and less than 5% decline (n = 40). There was a significant decline in Hct postbiopsy, with a linear correlation between the decrease in Hct at 6 and 24 hours (R2 = 0.47; P < 0.0001), suggesting that the former was a predictor of the latter. There was a linear correlation between the number of passes and number of cores obtained for the first four passes, but an inverse correlation when five passes or greater were required. Interestingly, there was no correlation between bleeding (>10% decline in Hct) and the number of passes or cores obtained. Gross hematuria and blood transfusion requirement were each encountered in three patients (3.6%). Importantly, the prebiopsy clinical diagnosis was altered in 18 of 59 native kidney biopsies (33%) and 10 of 24 transplant biopsies (41%). We conclude that percutaneous renal biopsy using an automated spring-loaded gun device coupled with ultrasound guidance is a safe technique and provides essential clinical information. Importantly, patients with a stable Hct at 6 hours were at low risk for bleeding at 24 hours while hospitalized. It remains to be determined if these findings could be extrapolated to early discharge from hospital.
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Affiliation(s)
- P Khajehdehi
- Division of Nephrology, Saint Louis University School of Medicine, St Louis, MO, USA
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Schroeder TJ, Moore LW, Gaber LW, Gaber AO, First MR. The US multicenter double-blind, randomized, phase III trial of thymoglobulin versus atgam in the treatment of acute graft rejection episodes following renal transplantation: rationale for study design. Transplant Proc 1999; 31:1S-6S. [PMID: 10330958 DOI: 10.1016/s0041-1345(99)00092-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/16/2022]
Abstract
In this study intended to establish equivalence between two antibody therapies for acute rejection in kidney transplant recipients, it was important to develop a rigorous protocol. Assurance of the presence of acute rejection was imperative. Therefore, due to the lack of literature support for clinical assessment of renal dysfunction, histologic diagnosis of acute rejection was required for enrollment in the study. Likewise, supportive literature for a correlation between response to anti-rejection therapy and the severity of rejection lead to the decision that the study should be stratified by a measurement of rejection severity for which Banff criteria were used. Finally, quantification of the response to therapy was also measured against the available literature and a large, newly developed international database of kidney transplant rejection episodes (the Efficacy Endpoints database) where serum creatinine, expressed as a percentage of the baseline level at the time of rejection was shown to be the most effective, available clinical marker of rejection response. Therefore, the US Multicenter Phase III Trial for comparing Thymoglobulin to Atgam in the treatment of acute rejection exhibits a unique and detailed study design that could be implemented in future trials as well as in clinical practice to improve assessment of outcomes.
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Affiliation(s)
- T J Schroeder
- Department of Pathology, University of Cincinnati Medical Center, Ohio 45267-0714, USA
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de Fijter JW, Bruijn JA. Acute nonoliguric renal failure after renal transplantation. Am J Kidney Dis 1999; 33:166-9. [PMID: 9915285 DOI: 10.1016/s0272-6386(99)70276-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Affiliation(s)
- J W de Fijter
- Department of Nephrology, Leiden University Medical Center, The Netherlands
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Rush DN, Nickerson P, Jeffery JR, McKenna RM, Grimm PC, Gough J. Protocol biopsies in renal transplantation: research tool or clinically useful? Curr Opin Nephrol Hypertens 1998; 7:691-4. [PMID: 9864667 DOI: 10.1097/00041552-199811000-00012] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Early protocol biopsies of stable, well functioning renal allografts reveal a high prevalence of clinically unsuspected acute and chronic pathology. It is becoming increasingly apparent that these histopathological findings are both pathogenic and predictive of long-term allograft outcome. Therefore, protocol biopsies may be required for optimal post-transplant surveillance until non-invasive methods to detect allograft inflammation are developed.
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Affiliation(s)
- D N Rush
- Department of Medicine, Health Sciences Centre, Winnipeg, Manitoba, Canada. drushexchange.hsc.mb.ca
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