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Table of Contents
ORIGINAL ARTICLE
Year : 2019  |  Volume : 13  |  Issue : 3  |  Page : 164-168

Significance and safety of renal allograft biopsies: Experience from a tertiary care center in India


1 Department of Nephrology, SMS Medical College, Jaipur, Rajasthan, India
2 Department of Pathology, SMS Medical College, Jaipur, Rajasthan, India

Date of Submission02-May-2019
Date of Decision06-Jun-2019
Date of Acceptance12-Aug-2019
Date of Web Publication17-Sep-2019

Correspondence Address:
Dr. Pankaj Beniwal
6, New Heerabagh, Near Kalyan Dharmshala, SMS Hospital, Jaipur - 302 004, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_10_19

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  Abstract 


Introduction: Renal allograft biopsy is a useful tool in the presence of allograft dysfunction. There are many published studies regarding utility and safety of native kidney biopsies, whereas for allograft biopsies, data are scarce. Methodology: This retrospective analysis included all patients who underwent renal allograft biopsies from January 1, 2012, to December 31, 2017. Data were collected from patient records and interviews. Details regarding clinical indications, preprocedure rise in creatinine, urine analysis, periprocedure fall in hemoglobin, postprocedure hematoma in ultrasonography, and other complications were noted. Details of biopsy findings were analyzed. We noted the changes made in treatment after renal biopsies. Results: One hundred and seventeen (n = 117) patients underwent 150 renal biopsy procedures, with a mean age of 38.3 ± 11.6 years. Ninety-two (78.6%) were male. The majority (89.74%) of the patients received kidney from live donors. The most common indication for biopsy was acute allograft dysfunction (54%) with asymptomatic rise in creatinine (32.7%). In the first 15 days posttransplantation, the most common indication was delayed graft function (15.33%). Ninety percent of biopsies were adequate. For clinical diagnosis of acute allograft dysfunction, the most common pathological finding was active antibody-mediated rejection (AMR) in 14.49% patients. In the presence of chronic allograft dysfunction, the most common histopathological finding was chronic AMR in 18 (13.04%) biopsies. Major complications occurred in 4.0% of patients. Conclusion: Renal allograft biopsy is a useful tool in the evaluation of allograft dysfunction, and with current biopsy technique under real-time sonography, the major complication rate is less. It can be regarded as a safe procedure with excellent diagnostic yield.

Keywords: Allograft biopsy, indication, safety


How to cite this article:
Gaur N, Malhotra V, Agrawal D, Singh SK, Beniwal P, 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 J Transplant 2019;13:164-8

How to cite this URL:
Gaur N, Malhotra V, Agrawal D, Singh SK, Beniwal P, 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 J Transplant [serial online] 2019 [cited 2019 Dec 11];13:164-8. Available from: http://www.ijtonline.in/text.asp?2019/13/3/164/266939




  Introduction Top


For patients with end-stage renal disease, kidney transplantation has been described as optimal treatment. In India, much advancement has been made in the area of kidney transplantation in the past 45 years. In this highly populated developing country, approximately 151–232 per million population are in need of kidney transplantation.[1] The estimation is that almost 220,000 people require kidney transplantation in India, but at present, only approximately 7500 kidney transplantations are performed at 250 kidney transplant centers in India.[2] Due to nonexistence of the National Transplant Registry, data are not as accurate as desirable.

Since the initial description of the percutaneous renal biopsy in 1951 by Iversen and Brun[3] and subsequent modifications by Kark and Muehrcke,[4] it has remained an integral procedure for the field of nephrology. In the presence of allograft dysfunction, allograft biopsy is the “gold standard” procedure for diagnosis and prognosis once vascular and surgical causes have been ruled out. The indications and threshold to perform transplant biopsy are not standardized, and different centers use their own protocols which include either protocol biopsy (at specified time) or indicated biopsy in the presence of allograft dysfunction.[5] Information on the reasons for initiating a biopsy could be helpful for developing more standardized guidelines for transplant biopsy.

Transplant biopsy is an invasive procedure with major complications comprising hemorrhage requiring blood transfusions, intra-arterial embolization, or surgical intervention.[6],[7]

Apart from complications, biopsy adequacy is also an important aspect. “Adequate” specimen is defined as a biopsy with ten or more glomeruli and at least two arteries, and for a minimal sample, at least seven glomeruli and one artery are needed.[8] The characteristics of a successful procedure are not only safety and adequacy but also its diagnostic yield.

In this study, we analyzed indications, complications, and adequacy of renal allograft biopsies performed at our center. We also assessed whether histopathological diagnosis provided by kidney biopsy matched the clinical provisional diagnosis and what impact histopathological diagnosis made on line of treatment.


  Methodology Top


This retrospective analysis included all patients who underwent percutaneous renal allograft biopsies from January 1, 2012, to December 31, 2017, at the Department of Nephrology and Renal Transplant, Sawai Man Singh Medical College, Jaipur, Rajasthan, India. Data were obtained from the departmental renal transplant patient database and from the patients' records. A detailed history was taken regarding basic disease, pretransplant and posttransplant course, and indication of biopsy from each patient. All patients had laboratory blood tests including complete blood count, renal function test, urine routine examination, prothrombin time–activated partial thrombin time, bleeding time, clotting time, and transplant kidney ultrasonography with Doppler studies prior to allograft biopsy. The rise in creatinine from baseline to the time of biopsy was based on a comparison of the nadir creatinine within the past 6 months and last creatinine preceding or on the biopsy date.

Transplant biopsies were performed under ultrasound guidance with 16–18G needles and a spring-loaded biopsy gun after informed consent in the supine position by a trainee nephrologist. As per our protocol, all patients were kept under observation for 24 h in transplant unit after the procedure with strict bed rest and regular blood pressure monitoring.

Before discharge, repeat ultrasound examination was done to look for hematoma formation. Hematocrit drop of >3% prompted for repeated hematocrit and/or further evaluation for hemorrhage.

A major complication of a renal transplant biopsy was defined as the need for additional hospitalization time and/or an active intervention. This included hospital admission, transfusion of blood products, interventional radiology vascular procedure, surgical exploration, transplant removal, and/or death.

Biopsy reports were noted and were matched against clinical provisional diagnosis. Biopsy was reported as per the Banff criteria 2013.[8] We documented the change in treatment done by the treating nephrologist after biopsy report and assessed the utility of renal allograft biopsies to improve patients' outcome by carefully noting the detailed follow-up of patients with renal function test and urine examination.

Statistical analysis

The data were entered into an Excel spreadsheet and analyzed using the SPSS software (SPSS Inc., Chicago, IL, USA). Summary categorical statistics were expressed as number (percentage). Summary continuous statistics were expressed as mean ± standard deviation if normally distributed or median (interquartile range [IQR]) if not.


  Results Top


Overall, 150 biopsies were performed in 117 patients in 5 years; 24 patients underwent procedure twice and 3 patients underwent thrice. All biopsies were indicated biopsies, and no protocol biopsy was performed. Mean age was 38.3 ± 11.6 years at the time of biopsy, with a male-to-female ratio of 92:25. The majority (n = 77 [65.81%]) of the patients had no known primary etiology for chronic kidney disease. Autosomal dominant polycystic kidney disease (7.69%) and diabetic nephropathy (7.69%) were the most common primary diseases, followed by immunoglobulin (Ig) A nephropathy (5.12%) [Table 1].
Table 1: Characteristics of patients undergoing renal allograft biopsy

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One hundred and five (89.74%) patients received kidney from live donors (parents/sibling/spouse/paired donation/ABO incompatible) and 12 (10.25%) patients received from deceased donors. Most of the patients had 2 (29.52%) or 3 (26.66%) human leukocyte antigen mismatches, and majority (62.39%) received injection methylprednisolone (500 mg 2 doses with 1-g intraoperative dose) along with capsule tacrolimus (0.1 mg/kg) and mycophenolate sodium (720 mg bd) without any antibody induction. The majority of the patients were on triple immunosuppression in the form of prednisolone (10 mg/day) (100%) + capsule tacrolimus (97.43%) + mycophenolate sodium (96.58%) [Table 1].

Median time from transplant to the first biopsy was 24 months (IQR: 2–61). Of 150 biopsies, 34 (22.66%) were performed within 15 days posttransplantation. Mean serum creatinine, mean rise in creatinine, and mean hemoglobin before biopsy were 2.4 ± 1.75 mg/dl, 1.62 ± 0.82 mg/dl, and 10.6 ± 0.76 g/dl, respectively.

Indication of renal allograft biopsy

Acute allograft dysfunction (54%) was the most common indication for which biopsy was performed; most patients had asymptomatic rise in creatinine (32.7%) (noticed on routine investigations), followed by proteinuria (17.33%). In the first 15 days posttransplantation, the most common indication was delayed graft function (15.33%) [Table 2].
Table 2: Indications for renal allograft biopsy

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Adequacy of biopsy

One hundred and thirty-five (90%) biopsies were adequate, whereas 1 (0.66%) was marginal, 2 (1.33%) were inadequate, and 12 (8%) had no renal tissue.

Histological findings

For clinical diagnosis of acute allograft dysfunction, the most common histopathological finding was active antibody-mediated rejection (AAMR) in 20 (14.49%) patients, followed by acute calcineurin inhibitor toxicity in 18 (13.04%) patients and acute tubular necrosis in 14 (10.14%) patients. In the presence of chronic allograft dysfunction, the most common histopathological finding was chronic AMR in 18 (13.04%) biopsies, followed by recurrence of disease in 15 (10.86%). Least incidence was of posttransplant lymphoproliferative disorder (0.72%) [Table 3].
Table 3: Adequacy and Histopathological diagnosis of renal allograft biopsy

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Correlation with clinical diagnosis

Overall, in 84.66% of cases, histopathological diagnosis matched the clinical provisional diagnosis. Changes were made in treatment according to biopsy findings including reduction in tacrolimus doses (13.33%), switching to sirolimus from tacrolimus (1.3%), steroid pulses (20.6%), injection antithymocyte globulin (13.33%), and steroid pulse with intravenous Ig with plasmapheresis (15.86%).

Complications

The most common complication was gross hematuria (7.33%), followed by hematoma (3.33%) formation noted on 24 h postprocedure ultrasonography. Major complications occurred in 4.0% of the patients which included blood transfusion in 2.66%, 1 (0.06%) patient needed allograft removal, and 1 (0.06%) patient expired postprocedure [Table 4].
Table 4: Complications associated with allograft renal biopsy

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  Discussion Top


Renal allograft biopsy has been regarded as a gold standard for allograft dysfunction after vascular and surgical causes have been ruled out. There are very few published data regarding renal allograft biopsy from India.

In our study, we found that the most common indication for allograft biopsy was acute allograft dysfunction (81.17%) with asymptomatic rise in creatinine (32.66%) as the most common clinical presentation. Recently published data from eastern India showed a similar finding of asymptomatic rise of creatinine as the most common clinical presentation.[9]

Only 8% of the biopsies had no tissue, whereas 90% of the biopsies were adequate.[8] This is comparable to other recently published studies which showed that 88% of transplant biopsies had >10 glomeruli.[10] However, in this study,[10] only 63% of biopsies were performed by fellow in comparison to our study where all biopsies were performed by nephrology residents (trainee fellow).

In our study, the most common pathological finding for acute allograft dysfunction was AAMR (14.49%). Various recently published studies showed comparable results with AAMR finding in 16.5%–24% of acute rejection biopsies.[11],[12] With better potent immunosuppression available in this era, the incidence of T-cell-mediated rejection has been controlled. AMR appears to be on the rise, likely secondary to changing trends in clinical practice, including selection of patients for transplantation with high risk and development of more effective combinations of immunosuppressive drugs against acute cellular rejection. Our finding is consistent with other studies published from India showing more incidences of AMR then T-cell mediated rejections.[13],[14] For chronic allograft dysfunction, the most common pathological finding was chronic rejection (chronic AMR + chronic AAMR). In a prospective study, the majority (63%) of the indication biopsy samples from renal allografts that failed after 12 months had evidence of chronic AMR.[15]

Histopathological diagnosis matched clinical diagnosis in the majority of the patients (61.33%). This is in contrast to that of Al-Awwa et al. who reported a poor correlation between clinical and histological diagnoses.[16] However, treatment was modified in 64.10% of patients following renal biopsy.

The success of any procedure depends on diagnostic yield as well as safety. The major complication rate in our study was 4% (blood transfusion, surgical intervention, and death) which is comparable to other studies [Table 5].[10],[17]
Table 5: Comparison of complications associated with renal biopsy reported in literature

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  Conclusion Top


Renal allograft biopsy is a useful tool in the evaluation of allograft dysfunction and must be performed whenever needed. With current biopsy technique under real-time sonography, the major complication rate is less and it can be regarded as a safe procedure with excellent diagnostic yield.

Acknowledgment

We would like to thank Dr. Vinay Rathore for his continuous guidance.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Modi G, Jha V. Incidence of ESRD in India. Kidney Int 2011;79:573.  Back to cited text no. 1
    
2.
Shroff S. Current trends in kidney transplantation in India. Indian J Urol 2016;32:173-4.  Back to cited text no. 2
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3.
Iversen P, Brun C. Aspiration biopsy of the kidney. Am J Med 1951;11:324-30.  Back to cited text no. 3
    
4.
Kark RM, Muehrcke RC. Biopsy of kidney in prone position. Lancet 1954;266:1047-9.  Back to cited text no. 4
    
5.
Broecker V, Mengel M. The significance of histological diagnosis in renal allograft biopsies in 2014. Transpl Int 2015;28:136-43.  Back to cited text no. 5
    
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Morgan TA, Chandran S, Burger IM, Zhang CA, Goldstein RB. Complications of ultrasound-guided renal transplant biopsies. Am J Transplant 2016;16:1298-305.  Back to cited text no. 6
    
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Redfield RR, McCune KR, Rao A, Sadowski E, Hanson M, Kolterman AJ, et al. Nature, timing, and severity of complications from ultrasound-guided percutaneous renal transplant biopsy. Transpl Int 2016;29:167-72.  Back to cited text no. 7
    
8.
Haas M, Sis B, Racusen LC, Solez K, Glotz D, Colvin RB, et al. Banff 2013 meeting report: Inclusion of c4d-negative antibody-mediated rejection and antibody-associated arterial lesions. Am J Transplant 2014;14:272-83.  Back to cited text no. 8
    
9.
Patil MR, Divyaveer SS, Mahajan C, Choudhury AR, Dasgupta S, Sarkar D, et al. Spectrum of renal allograft biopsy: A five-year experience at a tertiary care center of Eastern India. Saudi J Kidney Dis Transpl 2018;29:930-8.  Back to cited text no. 9
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Whittier WL, Gashti C, Saltzberg S, Korbet S. Comparison of native and transplant kidney biopsies: Diagnostic yield and complications. Clin Kidney J 2018;11:616-22.  Back to cited text no. 10
    
11.
Botermans JM, de Kort H, Eikmans M, Koop K, Baelde HJ, Malla MJ, et al. Risk factors for capillary C4d deposition in kidney allografts: evaluation of a large study cohort. Transplantation 2004;78:447-52.  Back to cited text no. 11
    
12.
Zhang J, Qiu J, Chen GD, Wang CX, Wang C, Yu SJ, et al. Etiological analysis of graft dysfunction following living kidney transplantation: A report of 366 biopsies. Ren Fail 2018;40:219-25.  Back to cited text no. 12
    
13.
Nigam LK, Vanikar AV, Kanodia KV, Patel RD, Suthar KS, Patel HV, et al. C4d-negative antibody-mediated rejection: A pathologist's perspective and clinical outcome. Saudi J Kidney Dis Transpl 2018;29:39-49.  Back to cited text no. 13
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14.
Gupta KL, Pattanashetti N, Sharma A, Ramachandran R, Nada R, Agarwal R, et al. Renal Transplant And Its Outcomes- Single Center Experience From India. Exp Clin Transplant. 2019 Jan;17(Sup1):78-82.  Back to cited text no. 14
    
15.
Einecke G, Sis B, Reeve J, Mengel M, Campbell PM, Hidalgo LG, et al. Antibody-mediated microcirculation injury is the major cause of late kidney transplant failure. Am J Transplant 2009;9:2520-31.  Back to cited text no. 15
    
16.
Al-Awwa IA, Hariharan S, First MR. Importance of allograft biopsy in renal transplant recipients: Correlation between clinical and histological diagnosis. Am J Kidney Dis 1998;31:S15-8.  Back to cited text no. 16
    
17.
Tsai SF, Chen CH, Shu KH, Cheng CH, Yu TM, Chuang YW, et al. Current safety of renal allograft biopsy with indication in adult recipients: An observational study. Medicine (Baltimore) 2016;95:e2816.  Back to cited text no. 17
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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