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Saudi Journal of Kidney Diseases and Transplantation
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RENAL DATA FROM THE ARAB WORLD Table of Contents   
Year : 2002  |  Volume : 13  |  Issue : 1  |  Page : 71-76
Renal Transplant Pathology: Bahrain Experience


1 Department of Pathology, Salmaniya Medical Complex, Manama, Bahrain
2 Department of Nephrology, Salmaniya Medical Complex, Manama, Bahrain
3 Transplantation Units, Salmaniya Medical Complex, Manama, Bahrain

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   Abstract 

A ten-year retrospective study on renal transplant biopsies performed at the Salmaniya Medical Complex, Bahrain was performed. The histological changes were classified according to Banff 1997 working classification of renal allograft pathology. A semi quantitative scoring was also given as per the guidelines. Out of a total of 26 cases, 10 belonged to hyperacute and acute forms, while 11 could be categorized to chronic sclerosing allograft nephropathy. In the remaining five, the graft pathology was unrelated to the rejection process. Despite effective management, four cases underwent nephrectomy due to severe vascular rejection. An interesting feature was recorded in two cases in whom transmural arteritis followed chronic histological changes. Presence of tubular atrophy and interstitial matrix increase were considered useful parameters for assessing the severity in cases with chronic allograft nephropathy.

Keywords: Renal transplant, Pathology and Banff classification, Acute rejection, Chronic rejection.

How to cite this article:
Ratnakar K S, George S, Datta B N, Fayek A, Rajagopalan S, Fareed E, Al Tantawi M, Al Arrayed S, Al Arrayed A. Renal Transplant Pathology: Bahrain Experience. Saudi J Kidney Dis Transpl 2002;13:71-6

How to cite this URL:
Ratnakar K S, George S, Datta B N, Fayek A, Rajagopalan S, Fareed E, Al Tantawi M, Al Arrayed S, Al Arrayed A. Renal Transplant Pathology: Bahrain Experience. Saudi J Kidney Dis Transpl [serial online] 2002 [cited 2019 Aug 23];13:71-6. Available from: http://www.sjkdt.org/text.asp?2002/13/1/71/33802

   Introduction Top


Bahrain, an independent state in the Middle East Gulf Region, has health services from primary to tertiary medical care. The annual incidence of end-stage renal disease (ESRD) in Bahrain is estimated to be around 120 per million population and both dialysis and transplantation services are available to care for these patients. [1] The etiology of ESRD is variable and diabetes mellitus (DM) ranks first. [2] A renal transplantation unit with all the necessary infrastructure including tissue typing laboratory and pathology services, is available since 1995. Todate over 57 patients have received renal allografts, all from live related donors, and managed according to international protocols.

Despite availability of various regimens to prolong the renal graft survival, early or late rejection continues to pose problems. [3],[4] In the living related transplants, about 27% and 40% of graft loss has been attributed to acute and chronic rejection, respectively. [3],[4] Early acute rejection phenomena, occurring generally within six months of transplan­tation, exhibit varying degrees of recovery with some unable to recover even with effective anti-rejection therapy. [5],[6] The prog­ressive deterioration in graft function that occurs late, termed chronic allograft neph­ropathy, is both pathogenetically and patho­logically different from the acute process [4] .

The Banff schema have been developed to categorize the post-transplant renal pathology with a view to develop clinicopathological correlation for assessment of treatment and understanding the pathobiology. [7] In this report, we present the pathology spectrum in the allografts which showed dysfunction, at the Salmaniya Medical Centre, a tertiary care hospital in Bahrain.


   Materials and Methods Top


A retrospective study was carried out on a total of 26 biopsies including five neph­rectomy specimens. The Banff 1997 working classification on allograft pathology was used by two independent observers. The biopsies were performed when there was renal dysfunction, fulfilling the indications for biopsies in transplant recipients. In addition to the routine hematoxylin and eosin stains, the sections were subjected to special stains such as PAS, reticulin, Verhoeff (elastic) and PTAH (fibrin).


   Results Top


All the biopsies included for analysis were adequate for interpretation. The results are given in [Table - 1],[Table - 2],[Table - 3],[Table - 4],[Table - 5]. A total of nine cases under the category of Banff acute/active rejection (category 4) were encountered [Table - 3]. Under grade IA and grade IIA, there was one case each, in grade IB there were three cases and there were four cases in grade III. All the cases belonging to grade III were nephrectomy samples, which revealed massive hemorrhagic infarction with histologically demonstrable transmural arteritis. These florid changes occurred beyond 18 months following transplantation [Figure - 3]. Three of these had undergone graft biopsies earlier; two showed changes of chronicity (category 5) while one showed acute changes (grade IA).

There were 11 cases showing chronic changes (category 5), of whom eight had grade II, one case had grade Ib and two had grade III changes. The features of chronicity included varying degrees of tubular loss with fibrosis.

While rejection process was the cause of graft failure in 21 cases, the etiology was different in the remaining five cases [Figure - 5],[Figure - 6]; recurrence of primary disease (FSGS) occurred in two while, technical failure, scleroderma with hypertension and membranous glomerulonephritis was seen in one case each.

We noticed that the acute rejection process showed tubulitis with interstitial inflam­mation [Figure - 1] and no vascular lesion in four cases, while in others, the vascular lesion was intense (v3) that compelled graft nephrectomy.

The tubulitis and onset of renal dysfunction did not show significant correlation with the number of inflammatory cells noticed in the tubular cross section. Severity of the tubulitis (category 4) ranged from t2 (five out of nine cases) to t3 (four out of nine cases). It is interesting to note that all t3 cases except one showed severe vascular changes v3. Sequential biopsies carried out in selected patients showed progression of lesions over a period varying from 12 to 18 months. The successive biopsies (four cases) showed both variability and severity. Chronicity (category 5, II and III) was seen in two cases, which was superimposed on acute phenomenon (category 4 III) in both the cases. In the remaining two cases, the pathology progressed in the same category (category 4) from I A to III in one. In the second, there was a shift in category from 2 to 4. This observation poses questions with regard to the applicability of Banff schema to predict the prognosis. Of the chronic allograft nephropathy cases analyzed in this series, two cases belonged to grade I, seven cases belonged to grade II and two cases to grade III. The specific sclerosing changes such as glomerular and vascular changes were encountered in four cases (4/11). There was no variation amongst the series to predict the glomerular or vascular changes with the duration of graft survival or the onset of graft dysfunction [Table - 3].


   Discussion Top


The Banff (1997) working classification of renal allograft pathology has been developed for standardization of biopsy interpretation, to guide therapy and establish objectivity for clinical trials. [7] A semiquantitave scoring has also been suggested taking into consideration the involvement of various components of renal biopsy namely tubular, vascular, interstitial and glomerular units.

The current (Banff 1997) classification is a development over the last, based on the inputs drawn from the Banff schema published earlier and the collaborative clinical trials in transplantation (CCTT) modification for diagnosis of renal allograft pathology. [7]

The age at the time of transplant in the present report varied from 16-67 years with equal sex distribution. There was no specific causative factor identifiable to account for the renal dysfunction in the graft and the live related donors, as expected, did not have any gross abnormality. The interval between transplantation and biopsy, irrespective of the histological changes, was extremely variable from three months to five years, and in five cases the pathology was unrelated to rejection.

In one case, there was antibody-mediated rejection of accelerated acute type (delayed) with large number of glomeruli distended with sequestrated platelets. Acute terminal process of transmural arteritis occurred in four cases and all ended with graft neph­rectomy. Tubulitis was noticed in one patient who developed vascular rejection after 18 months of effective management. In the remaining three cases, the previous biopsies showed progressive widening of interstitium with tubular atrophy, but developed vascular rejection necessitating nephrectomy within one year of onset of renal dysfunction and first biopsy. Pathogenetically, these cases are distinct indicating that the vascular rejection may occur at any period of the graft life while initial cause of graft dysfunction could be mild to moderate, acute or chronic form. This requires serious attention in view of the primary biopsy not truly assisting in the prediction of the behavior of the graft. Factors such as non­compliance with medical therapy, cyclos­porine toxicity and infection could all be contributing to the survival of the renal graft. Immunohistological evaluation of the infiltrating cells for MHC class II, IL2 receptor and cytokine assessment are likely to help to guide the therapy and predicting the rejection process. [9]

In the chronic sclerosing allograft nephro­pathy group, the onset of renal dysfunction was from nine months to five years. The quantitative scoring revealed a correlation between tubular atrophy and interstitial fibrosis with no correlation with vascular and glomerular lesions. Therefore, these two parameters are of immense importance in the chronic phase of graft failure. The double contour glomerulopathy and sub­endothelial hyalinization with neointima formation, attributed to chronic transplant pathology, was encountered in five cases and these patients still have a functioning graft on the date of reporting the series. As has been observed by many, tubular atrophy and interstitial fibrosis may be patho­genetically complex and maybe somewhat unrelated to immune rejection process. [10],[11],[12] There is no distinct difference in the severity or stage of allograft function with the histology of chronic lesions in the t2 and t3 stages. Larger series and careful follow up would show the significance of these parameters in the future. No conclusion can be drawn on the influence of management in the present series as the cases have been treated as per the standard protocols.

The primary aim of this presentation is to place on record the spectrum of histological changes encountered in the Transplant Unit at Bahrain, along with the peculiarities in the lesions noticed in the sequential biopsies.

 
   References Top

1.Al Arrayed A, Al Tantawi M, Fareed E, Haider F, Abouna G. Renal transplant in Bahrain. Bahrain Medical Bulletin 2000; 22(2):63-6.  Back to cited text no. 1    
2.Al Mahroos F, Mckeigue PM. High preva­lence of diabetes in Bahrainis. Associations with ethnicity and raised plasma cholesterol. Diabetes Care 1998;21:936-42.  Back to cited text no. 2    
3.Sayegh MH, Carpenter CB, Bennet WM, Vella JP. Acute renal allograft rejection: treatment. Up To Date 1999;7(3):1-6.  Back to cited text no. 3    
4.Paul LC. Chronic allograft nephropathy: an update. Kidney Int 1999;56:783-93.  Back to cited text no. 4    
5.Lindholm A, Ohlman S, Albrechtsen D, et al. The impact of acute rejection episodes on long term graft function and outcome in 1347 primary renal transplants treated by 3 cyclosporine regimens. Transplantation 1993;56:307-15.  Back to cited text no. 5    
6.Burke JF Jr, Pirsch JD, Ramos EL, et al. Long-term efficacy and safety of cyclos­porine in renal transplant recipients. N Engl J Med 1994;331:358-63  Back to cited text no. 6    
7.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. 7    
8.Sayegh MH, Vella JP, Carpenter CB. Acute renal allograft rejection: diagnosis. Up To Date 1999;7(3):1-4.  Back to cited text no. 8    
9.Hancock WW. Analysis of intra-graft effector mechanisms associated with human renal allograft rejection: immuno­histological studies with monoclonal antibodies. Immunol Rev 1984;77:61-84.  Back to cited text no. 9    
10.Peschke B, Scheuermann EH, Geiger H, Bolscher S, Kachel HG, Lenz T. Hyper­tension is associated with hyperlipidemia, coronary heart disease and chronic graft failure in kidney transplant recipients. Clin Nephrol 1999;51:290-5.  Back to cited text no. 10    
11.Kasiske BL. Clinical correlates to chronic renal allograft rejection. Kidney Int 1997; 63(Suppl):S71-4.  Back to cited text no. 11    
12.Katznelson S, Gjertson DW, Cecka JM. The effect of race and ethnicity on kidney allograft outcome. Clin Transpl 1995:379-94.  Back to cited text no. 12    

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Correspondence Address:
K S Ratnakar
Department of Pathology, Salmaniya Medical Complex, P.O. Box 12, Manama
Bahrain
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PMID: 18209419

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    Figures

  [Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6]
 
 
    Tables

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



 

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    Materials and Me...
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