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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 2003  |  Volume : 14  |  Issue : 1  |  Page : 18-22
Role of Sequential Biopsy Study in the Evaluation of Renal Transplant


1 Department of Pathology, Salmaniya Medical Centre, Manama, Bahrain
2 Department of Nephrology, Salmaniya Medical Centre, Manama, Bahrain

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   Abstract 

Renal biopsy is indicated in all cases of renal transplants showing renal dysfunction. This not only helps in the diagnosis but also in the institution of proper management. Study of sequential biopsies is essential for establishing the cause of renal dysfunction, evaluation of the effect of treatment and the progress of the disease. This report is based on the study of 14 samples (including three nephrectomy specimens) belonging to six patients who underwent two or more sequential renal transplant biopsies at the Salmaniya Medical Centre, Bahrain, between 1995-2000 because of deteriorating renal functions. Based on the sequential biopsies, the graft dysfunction was attributed to rejection in four cases and recurrence of primary glomerular disease in two. An important finding in this series is one case of type I membranoproliferative glomerulonephritis due to hepatitis C noticed five years after transplant and two cases of acute vascular rejection superimposed upon chronic rejection.

Keywords: Rejection, Renal biopsy, Renal Transplantation, Transplant pathology.

How to cite this article:
Ratnakar KS, Al Hilli F, George SM, Al Arrayed S, Al Arrayed A. Role of Sequential Biopsy Study in the Evaluation of Renal Transplant. Saudi J Kidney Dis Transpl 2003;14:18-22

How to cite this URL:
Ratnakar KS, Al Hilli F, George SM, Al Arrayed S, Al Arrayed A. Role of Sequential Biopsy Study in the Evaluation of Renal Transplant. Saudi J Kidney Dis Transpl [serial online] 2003 [cited 2020 Dec 4];14:18-22. Available from: https://www.sjkdt.org/text.asp?2003/14/1/18/33083

   Introduction Top


Graft failure occurs primarily due to immunological rejection or recurrence of disease despite effective pre- and intra­operative management. [1] Choosing an appro­priate HLA-matched donor and effective immunotherapy reduces the incidence of graft rejection. However, recurrence of the primary disease continues to pose a problem in the management of renal transplantation even with live related donors. Deterioration in the renal function alerts the physician towards the onset of graft failure but biopsy alone provides direction towards further management. [2] Therefore, the histopatholo­gical study of the renal biopsies is important to establish the definite diagnosis of such cases and also provides information on the progress of the disease process. The role of sequential biopsies cannot be over-emp­hasized in view of the information obtained on evaluation of the disease as well as the influence on treatment administered. We present in this study the pathological findings on sequential biopsies on renal transplants carried out in Bahrain between 1995 and 2000.


   Patients and Methods Top


A retrospective analysis was carried out on six patients who underwent two or more sequential renal allograft biopsies in the Department of Nephrology, Salmaniya Medical Centre, Bahrain between 1995 and 2000. The indication for biopsy was deterioration of allograft function. There were 11 biopsies and three nephrectomy specimens and all were processed for routine hematoxylin and eosin stains in addition to Periodic Acid Schiff (PAS) and Jones stains.

All adequate biopsy specimens (at least seven to ten glomeruli and one to two arterioles) that showed features of rejection, were analyzed and categorized according to Banff schema 1999. [3] The nephrectomy specimens were carefully examined for the anatomical distribution of lesions in the vascular and parenchymal compartments.

Laboratory investigations including hema­tological and biochemical tests were carried out and corroborated with clinical and histological findings.


   Results Top


[Table - 1] shows the age and sex distribution of patients, the pathologic Banff cate­gorization, the duration of illness following transplantation, the intervals of sequential biopsies and the outcome of the transplants. Two cases showed glomerular disease, one of which was recurrence and the other de novo disease in the post-transplant period.

In a 19-year-old female (case 5), focal segmental glomerulosclerosis (FSGS) recurred one month following transplantation and sequential biopsies carried out at five and 15 months interval [Figure - 1] also confirmed the recurrence. Progressive deterioration of renal functions necessitated dialysis in this case and the patient continues to be on this modality of treatment at last follow-up.

The second case occurred in a 42-year-old male (case 6) who underwent transplant for end stage renal disease following idiopathic membranoproliferative glomerulonephritis (MPGN). The MPGN recurred at the end of five years and serology demonstrated the presence of hepatitis C [Figure - 2]

The remaining four cases revealed rejection process at various intervals despite the usage of the best immunosuppression protocols. The HLA typing and crossmatch was acceptable in all cases and all transplants were from live related donors. The rejection process of different types of Banff category occurred at varying periods, ranging from two days to twenty-four months following transplantation.

The earliest rejection episode occurred in a 46-year-old female (case 4), who had a graft biopsy at two days post-transplantation. The histological picture was that of glomerular distension with platelet thrombi indicating delayed (accelerated acute) antibody-mediated rejection (Banff category 2). The second biopsy performed 12 days later showed cellular rejection (tubulitis) while renal dysfunction continued.

Chronic rejection process in terms of tubular atrophy and interstitial fibrosis of mild degree was noticed in one patient (case 1), and this progressed to severe degree of acute vascular rejection that led to graft nephrectomy [Figure - 3]. One patient (case 3) had Banff category 5 changes (chronic), with the pathology showing transplant glomerulopathy with membra­noproliferative morphology in addition to tubulointerstitial alterations. In one year's time, this case progressed to acute vascular rejection that led to graft nephrectomy.

One case of acute rejection (case 2), which occurred three months following transplan­tation showed tubulitis (Banff 4IA). This patient continued to have good graft function for eighteen months when the patient developed acute vascular rejection.


   Discussion Top


This report illustrates the importance of sequential biopsies, not only for diagnosis but also for the evaluation of the progress of the rejection process. [4] Four cases revealed rejection process of acute or chronic type. Despite compatible HLA matching, rare cases of antibody mediated rejection, which occurs within the first few hours or days of transplantation are documented. The typical histopathology of glomerular distension with platelet thrombi in the absence of any demonstrable antibody raises the possibility of endothelial antigens participating in a similar event. To date, there are no definite laboratory tests available for evaluation of endothelial antibody mediated rejection. [5]

Chronic transplant nephropathy is generally noticed in a patient by a decline in renal allograft function after the initial three months following transplant. [6] Histologically, the changes are centered principally around the tubulointerstitial compartment with or without glomerular or arteriolar changes. Membranoproliferative glomerular alterations with or without neointimal changes in the vessels are considered typical of chronic transplant nephropathy. [3]

Such morphology was noticed in one case in the present series at the end of twenty­four months of transplantation. In another case, tubular atrophy with interstitial scarring observed nine months following transplant, progressed to show specific glomerular changes in the next thirteen months even with adequate immunosuppression. Both cases ended in acute rejection of vascular type (Banff 4 grade III), which is an uncommon behavior of chronic transplant nephropathy resulting in nephrectomy. The progress of the lesions to acute vascular rejection occurred at variable periods of one to twelve months after receiving identical protocols of management. It is therefore difficult to predict the progression as well as explain the pathomechanism. It is possible that the vascular rejection mechanism is independent and may occur at any stage of post-transplant period. The influence of drugs on the type of rejection process is difficult to assess, as the mechanisms are different.

Case two in the present series showed acute rejection with mild renal dysfunction at three months after transplantation. This progressed to vascular rejection in the next fifteen months period despite aggressive immunosuppression. Essentially, humoral mechanisms play a major role in acute vascular rejection. The factors that are responsible for the onset of the lesion are difficult to predict.

Focal segmental glomerulosclerosis is one of the morbid disorders known to affect the graft. [7] The recurrence rate cited varies from 5-100% and nearly 30-50% graft loss has been recorded due to recurrence of FSGS. The etiological initiators of FSGS as well as factors responsible for recurrence are largely elusive. The roles of humoral factors and hyperfiltration have been suggested. Membra­noproliferative glomerulonephritis occurred at the end of five years of transplantation in one case. The MPGN morphology may be considered as part of chronic transplant nephropathy. However, serological investi­gations at this time revealed the patient to be positive for hepatitis C. As there were no associated or proportionate tubulointerstitial alterations, this case was considered as primary glomerular disease developing due to hepatitis C. Immunofluorescence studies revealed intense C3 positivity with moderate IgM positivity. This pattern suggests the case to be Type I MPGN and not transplant glomerulopathy. [8],[9] Also, sub-endothelial electron dense deposits demonstrated ultrastructurally supports the diagnosis of primary glome­rular disease.

The present report highlights the spectrum of changes noticed in sequential allograft biopsies and the morbid sequelae that followed in few cases. This report also emphasizes the deve­lopment of acute rejection of severe form on the background of chronic rejection, little emphasized hitherto in previous reports.


   Acknowledgement Top


The authors wish to thank Dr. Ali A Satir, Chairman, Department of Pathology and Dr. Adel Al Jishi, Chairman, Department of Internal Medicine for granting permission to place these cases on record.

 
   References Top

1.Racusen LC, Solez K, Olseus. The pathology of kidney transplantation. In: Kidney Trans­plant Rejection (Vol 3). Racusen LC, Solez K, Burdick JF, (Eds). New York Marcel Dekker 1998;pp383-418.  Back to cited text no. 1    
2.Gaber LN, Moore LW, Alloway RR, et al. Correlation between Banff classification, acute renal rejection scores and reversal of rejection. Kidney Int 1996;49:481-7.  Back to cited text no. 2    
3.Racusen LC, Solez K, Colvin RB, et al. The Banff 97 working classification of renal allograft pathology. Kidney Int 1999; 55:713-23.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]
4.Rush DN, Jeffrey JR, Gough J. Sequential protocol biopsies in renal transplant patients: Clinicopathological correlations using the Banff schema. Transplantation 1995;59:511-4.  Back to cited text no. 4    
5.Demirhan B, Karakayali H, Turan M, Gungen Y, Bilgin N. Hyperacute allograft rejection mediated by IgM antibodies and a negative lymphocyte crossmatch: Report of two cases. Transplant Proc 1998;30:732-3.  Back to cited text no. 5    
6.Paul LC. Chronic allograft nephropathy: An update. Kidney Int 1999;56:783-93.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]
7.Striegel JE, Sibley RK, Fryd DS, Maner M. Recurrence of focal segmental sclerosis in children following renal transplantation. Kidney Int Supplement 1986;19:S44.  Back to cited text no. 7    
8.Svetlozar Natov, Pereira BJ. Renal disease associated with Hepatitis C virus after renal transplantation. Up To Date 2000;8(1):1-4.  Back to cited text no. 8    
9.Andresdottir MB, Assman KJ, Koene RA, Wetzeis J. Immunohistological and ultra­structural differences between recurrent Type I MPGN and chronic transplant glomerulopathy. Am J Kidney Dis 1998; 32(4):582-8.  Back to cited text no. 9    

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Correspondence Address:
Kamaraju Suguna Ratnakar
Department of Pathology, Salmaniya Medical Centre, P.O. Box 12, Manama
Bahrain
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PMID: 17657085

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    Abstract
    Introduction
    Patients and Methods
    Results
    Discussion
    Acknowledgement
    References
    Article Figures
    Article Tables
 

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