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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE  
Year : 2012  |  Volume : 23  |  Issue : 4  |  Page : 701-706
Effect of lymph leakage on renal allograft outcome from living donors


1 Department of Transplantation; Department of Urology, Tabriz University (Medical Sciences), Tabriz, Iran
2 Drug Applied Research Center, Tabriz University (Medical Sciences), Tabriz, Iran
3 Department of Transplantation, Tabriz University (Medical Sciences), Tabriz, Iran
4 Medical Researches, Tabriz University (Medical Sciences), Tabriz, Iran

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Date of Web Publication9-Jul-2012
 

   Abstract 

Lymph leakage is a cause of prolonged fluid discharge in renal transplant patients. Lymph leakage during early post-transplantation is responsible for extracting immune substances; therefore, it may play a role in prognosis of the transplanted kidney. In this study, we aimed to investigate the effects of lymph leakage on different factors that play significant roles in renal allograft outcome. During the present case-control study, we evaluated 62 renal allograft recipients in which 31 subjects were complicated with lymph leakage and enrolled as the study group. The other 31 subjects were included in the control group who did not experience any lymph leakage during their post-transplantation period. All kidneys were transplanted from living donors. We investigated and compared the renal allograft rejection rate, hospitalization duration, serum urea, creatinine (Cr) and cyclosporine (CsA) levels, antithymoglobin (ATG) administration and treatment duration between the study and the control groups. There were no significant difference in the urea and Cr levels between the two groups (P >0.05). Early (one week) and late (one month) serum CsA levels of the study group were significantly higher than in the control group (P = 0.005 and P = 0.006). The number of days in which ATG receivers responded to therapy was significantly lower for the control group (P = 0.008). 21.93% of the study group subjects experienced allograft rejection, while this rejection probability was 28.38% for the control group (P = 0.799). Lymph leakage has no prominent role in renal function, which is estimated by Cr and urea levels in patients' serum during the days after transplantation. CsA level was higher in patients with lymph leakage, and all cases of allograft rejection were in the subjects with lymph leakage.

How to cite this article:
Bohlouli A, Nezami N, Zomorrodi A, Abdollahifard S, Hashemi B. Effect of lymph leakage on renal allograft outcome from living donors. Saudi J Kidney Dis Transpl 2012;23:701-6

How to cite this URL:
Bohlouli A, Nezami N, Zomorrodi A, Abdollahifard S, Hashemi B. Effect of lymph leakage on renal allograft outcome from living donors. Saudi J Kidney Dis Transpl [serial online] 2012 [cited 2020 Mar 28];23:701-6. Available from: http://www.sjkdt.org/text.asp?2012/23/4/701/98113

   Introduction Top


Continued improvements in graft survival have led to widespread acceptance of renal trans­plantation as the preferred treatment for the majority of patients with end-stage renal di­sease (ESRD). [1] Besides its vital benefits, renal transplantation is associated with some complications. As one of transplantation complica­tions, lymphatic leak is a cause of prolonged fluid discharge in kidney precipitants in whom early recognition and therapy is essential for the survival of the kidney. [2] Prolonged lymph drainage is an undesirable complication follo­wing kidney transplantation. [3] Lymph leakage occurs from the large number of lymphatic vessels present in the retroperitoneal area sur­rounding the iliac artery and vein. Failure to ligate these vessels at the time of transplan­tation may lead to prolonged drainage of lymph. [4] Of the possible causes examined, dia­thermy and division of iliac lymphatics seems to be the most likely reason for lymph leakage. [5] It is believed that extensive peri-vas­cular dissection along the route of iliac vessels, episodes of acute rejection, cadaveric versus live donors, high doses of corticosteroid the­rapy, re-transplantation, and polycystic disease in the recipients are some of the factors that contribute to the development of fluid drainages. [6] Moreover, lymph leakage can result from traumatic or surgical transaction of lymph channels. As a result of the number, orienta­tion, and location of lymphatic vessels in the groin, renal transplant surgery in this region can result in lymphatic disruption. [2] Lymph lea­kage during the transplantation period is res­ponsible for extracting immune substances that consist of antigens, antibodies, complements, and immunosuppressant agents; therefore, it may play a diverse role in the prognosis of the transplanted kidney. Accordingly, it is of great importance to understand the probable patho­logic impact of lymph leakage on the outcome of transplanted kidney. Outcome after kidney transplantation has steadily improved over the past three decades, thanks to improvement in immunesuppression, anti-rejection therapy, organ retrieval techniques, peri-operative care, and treatment of post-transplant infectious complications. [7] However, there has not been any specific research done to determine and demonstrate the possible im­pressions of post-transplantation lymph leakage on prognosis of recipients' renal function. Whereas rejection nephropathy still remains the most serious problem in transplant medicine through T cell-dependent mechanisms, [8],[9] it seems likely that any lymphatic leakage may improve or even conversely worsen the immunosuppressive status of the recipient by conti­nuously emptying the produced materials of the immune system against the graft as well as the immunosuppressants. Generally, the success with which rejection can be reversed by immunosuppressive agents determines the chance of long-term success of the transplant. [10],[11] On the other hand, continued immunosuppression is inevitable for the long-term function of transplanted organs, and its objective is to prevent graft rejection while maintaining the immunity of the recipient. [8] For that reason, lymph leakage by draining out the antibodies as well as the antigens, complements, several types of cytotoxic cells, and immunosuppressant drugs directly from the immune system may decrease or even increase the anti-graft load on newly presented organ to the recipients' recognizer T cells. To the best of our know­ledge, this hypothesis has not been surveyed and established yet. This study is aimed to investigate several effects and interactions of lymph leakage on different factors that play a significant role in renal transplantation ma­nagement.


   Materials and Methods Top


This study was designed as a case-control study to evaluate the possible effects of lymph leakage on the post-transplantation renal func­tion in kidney recipients. We evaluated 62 renal allograft recipients in which 31 subjects were complicated with lymph leakage and were enrolled as the study group. Lymph leakage was defined as more than 50 mL daily fluid leakage from the drain with blood urea nitro­gen, creatinine, and potassium similar to those of the patient's serum, but significantly lower concentrations of calcium and protein. Patients who developed lymphocele were excluded from the study. The other 31 subjects were included in the control group, and included those who did not experience any lymph leakage during post-transplantation. All transplantation ope­rations were performed through July 2004 to August 2008 in the Imam Khomeini and Imam Reza Hospitals of Tabriz by the same trans­plantation team. All participants of both study and control groups were matched together based on their age, sex, and immunosuppressant regime [all receipts underwent combination therapy with prednisolone, cyclosporine A (Iminoral), and cellcept], and all received kid­ney from living donors. Patients with any other causes of rejection such as renal artery or vein thrombosis were excluded from the study.

A J-shaped incision (Gibson incision) was made in either the right or the left lower qua­drant. The epigastric vessels were divided and the spermatic cord retracted medially. The ex­ternal iliac vein and artery were mobilized, and lymphatic tissues overlying them were care­fully doubly ligated between ties before dis­section. After blunt mobilization of the peri­toneal sac, vascular anastomoses were per­formed in an end-to-side fashion. Hypogastric artery was used as the site for end-to-end anastomosis in case of graft from living related donor. The left kidney was usually implanted in the right iliac fossa and the right kidney in the left fossa.

The age and gender of the patients, panel test, blood group and Rh, hospitalization duration, rejection probability, need for anti-thymoglobulin (ATG) or anti-lymphocytes globulin (ALG) besides duration and answer to its adminis­tration, and prednisolone pulse therapy were evaluated and compared between the groups.

Serum level of creatinine (Cr) and urea were determined, respectively, by the Jaffe method (mg/dL) and commercial kit (mg/dL) 24 h after transplantation and at the time of dis­charge from the hospital.

All the patients received prednisolone, cyclosporine (CsA), and mycophenolate mofetil (MMF) regime. Serum CsA level was mea­sured by monoclonal radioimmunoassay (ng/dL) one week (early) and one month (late) after transplantation.

Finally, rejection rate was compared between the study and control groups. In addition, we analyzed, statistically, the effect of several va­riables that were evaluated in this study, on renal allograft rejection rate between the study and control groups.

Statistical analyses were performed by SPSS version 13.0 for windows software package (SPSS, Chicago, IL, USA). Results are pre­sented as mean values and standard deviation (SD). Statistical significance between groups was estimated using the independent sample t-test, Fisher exact test, or Chi square test. The results were considered significant when the P-value was less than 0.05.


   Results Top


The mean age of the patients was 43.26 ± 2.27 and 40.71 ± 2.39 years for the study and control groups, respectively (P = 0.444). The male to female ratio was 15:16 for both groups (P = 1.000). The prevalence of blood groups and Rh are listed in [Table 1] and [Table 2].
Table 1: Blood group distribution among patients of study and control groups.

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Table 2: Rh distribution among patients of the study and control groups (P = 0.612).

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The negative results of panel antibody tests for the study group (99.19% ± 0.46) and the control group (99.67% ± 0.32) were not dif­ferent in both groups (P >0.399).

The mean hospitalization days was 25.37 ± 9.78 days for the study group and 28.57 ± 6.98 days for the control group, which did not show a statistically significant difference (P = 0.806).

The serum levels of Cr and urea at 24 h after transplantation and the time of discharge are demonstrated in [Table 3]. There were no signi­ficant differences between the groups.
Table 3: Relation between study and control groups' creatinine and urea levels.

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Lymph leakage was 137.86 ± 45.19 and 22.52 ± 8.93 mL/day for the study and control groups at the first day after transplantation, respec­tively. Duration of leakage was 16.34 ± 5.25 and 9.60 ± 6.14 days for the study and control groups, respectively.

The mean early serum CsA levels in the study and control groups were, respectively, 200.51 ± 21.57 and 127.24 ± 12.93 ng/mL, and the early serum CsA level was significantly higher in the study group than in the control group (P = 0.005). Also, the study group had a significantly higher late serum level of CsA than the control group (260.84 ± 27.48 vs. 187.53 ± 17.52 ng/mL; P = 0.006).

Thirteen (21%) of 62 subjects received prednisolone pulse therapy, eight of which were in the study group and five belonged to the con­trol group. The number of patients who under­went pulse therapy was not statistically diffe­rent between the study and control groups (P = 0.534). The risk of rejection was 41.93% and 48.38% in the study and control groups, respectively, which also did not show a significant difference (P = 0.079). On the other extreme, none of the patients in the control group ex­perienced rejection, while 9.67% of the study group complicated with renal allograft rejec­tion. Comparison of the rejection rate between the groups show a significant difference (P = 0.023). In both the study and the control group, 11 patients (35.48% of each group) had been given ATG. All the patients who received ATG in the control group had responded successfully to the treatment, while only eight of 11 sub­jects from the study group presented optimal therapeutic response. The number of patients who underwent ATG therapy and the response rate to the treatment was not statistically diffe­rent between the groups (P = 1.000 and 0.214). However, duration in which ATG receivers responded to therapy was significantly lower in the control group (5.72 ± 1.36 vs. 10.90 ± 3.70 days; P = 0.008).


   Discussion Top


There was no statistically significant diffe­rence in demographic characteristics (age, gen­der, blood group, Rh, and the results of panel test) between subjects with lymph leakage and controls.

Although the present study revealed that kid­ney recipients with lymph leakage were hospi­talized for fewer days than recipients without lymph leakage, as it did not show a statis­tically significant difference, we cannot attri­bute this finding to the whole population of renal allograft recipients.

Serum Cr is the most useful measurement of renal function. [9] It is important to determine the admission Cr and its trend over the duration of hospitalization. [7] We evaluated the serum Cr and urea levels 24 h post-transplantation as well as at the time of discharge from hospital. Except the urea level in 24 h after transplanta­tion, there was no significant difference bet­ween kidney recipients with or without any lymph leakage. Although there are some re­ports that lymph leakage in some patients may lead to decrease in serum Cr level, [2] it seems likely that occurrence of lymph leakage has no prominent role in renal function estimated by serum Cr and blood urea levels.

CsA is still a widely used immunosuppressive agent for renal allograft recipients. [7] All 62 participants in this study received CsA as one of their maintenance immunosuppression re­gime. Serum CsA levels at first week (early) and first month (late) after transplantation were significantly higher in kidney recipients with lymph leakage as compared with the recipients without any lymphatic leak. In the study by Van Rijen et al [12] in 2002, the animal models with the highest level of CsA showed the highest number of CD154+ cells in their lymphoid tissue. This means that the CD154 molecule, which is essential for the initiation of organ allograft rejection, is expressed even more during CsA therapy in lymphatics. This event may be one of the etiological factors that lead to the higher rejection rate in study group.

Corticosteroids are one of the basic immunosuppressive drugs used after transplantation. [8],[13] Similarly, the number of patients needing prednisolone pulse therapy was higher among the kidney recipients with lymph leakage. How­ever, it was not statistically significant.

Although the present study was carried out with the initial hypothesis that draining out the immune materials during lymph leakage may partially protect the kidney recipient from re­jection, the results of the present study showed that all rejected allografts belonged to the kid­ney recipients with lymph leakage.

The experimental study of Pedersen and Bede [14] showed that the lymph draining a renal allograft increased, remarkably, the volume and number of proliferating lymphoblasts. In addi­tion, removing this lymph did not alter the course of acute graft rejection. This predicted the later unsuccessful attempts to prevent rejection by thoracic duct drainage. [15] Lymphocele and lymphatic fistulae are relatively benign complications in renal transplantation, but the main importance of these complications lies in acute rejection episode (i.e., high frequency of cellular rejection) with all it's therapeutic implications. [16],[17] However, patients with lymphocele were excluded from the present study be­cause of the possible mechanical effect, which may create bias in the study results.

ATG is used prophylactically as induction therapy during the early post-transplantation period and also for treatment of acute rejection. [18] In view of the fact that leak of lymph could result in the loss of various immune products as well as the immunosuppressant agents, we hypothesized that in patients who needed ATG administration, lymph leakage would have a double-edged impact on success­fully responding to the drug. Results of the present study indicate that among the kidney recipients who received ATG, those without lymph leakage recovered in significantly lo­wer number of days in comparison with those with lymph leakage.

The present, primary study results, show that occurrence of lymph leakage has no prominent role in renal function estimated by serum Cr and urea levels during the days after trans­plantation. As opposed to our initial hypothe­sis that draining out the immune materials may lead to reduction of rejection rate among recipients, all rejected allografts belonged to the kidney recipients with lymph leakage in this study.

 
   References Top

1.Akbar SA, Jafri SZ, Amendola MA, Madrazo BL, Salem R, Bis KG. Complications of Renal Transplantation. RadioGraphics 2005;25:1335-56.  Back to cited text no. 1
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2.Caglar M, Ergun EL. Lymphatic Leakage in a Renal Transplant: The Role of Lymphoscintigraphy. Clin Nucl Med 2006;31:486-9.  Back to cited text no. 2
    
3.Saidi RF, Wertheim JA, Ko DS, et al. Impact of donor kidney recovery method on lymphatic complications in kidney transplantation. Transplant Proc 2008;40:1054-5.  Back to cited text no. 3
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4.Kirkman RL, Tilney NL. Surgical Complications in the Transplant Recipient. In: Milford EL, Brenner BM, Stein JH, Eds. Renal Transplan­tation. New York: Churchill Livingstone; 1989. p.240.  Back to cited text no. 4
    
5.Griffiths AB, Fletcher EW, Morris PJ. Lymphocele after Renal Transplantation. ANZ J Surg 2008;49:626-8.  Back to cited text no. 5
    
6.Dubeaux VT, Oliveira RM, Moura VJ, Monteiro J, Pereira S, Henriques FP. Assesment of lymphocele incidence following 450 renal trans­plantations. Int Braz J Urol 2004;30:18-21.  Back to cited text no. 6
    
7.Humar A, Leone JP, Matas AJ. Kidney Trans­plantation: a brief review. Front Biosci 1997; 2:41-7.  Back to cited text no. 7
    
8.Breza J, Vavra Til P. Renal transplantation in adults. BJU Int 1999;84:216-23.  Back to cited text no. 8
    
9.Kanmaz T, Fechner JJ Jr, Torrealba J, et al. Monotherapy with the novel human anti-CD154 monoclonal antibody ABI793 in rhesus monkey renal transplantation model. Trans­plantation 2004;77:914-20.  Back to cited text no. 9
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10.Terasaki PI, Cecka JM, Gjertson DW, Takemoto S, Cho YW, Yuge J. Risk rate and long-term kidney transplant survival. Clin Transpl 1996; 443-58.  Back to cited text no. 10
    
11.Chan L, Kam I. Outcome and complications of renal transplantation. In: Schrier RW, Ed. Diseases of the Kidney. Gottschalk: CW; 1997.  Back to cited text no. 11
    
12.Van Rijen MM, Kuijf ML, Metselaar HJ, et al. CD154 is expressed during treatment with calcineurin inhibitors after organ transplan­tation. Transplantation 2002;73:1666-72.  Back to cited text no. 12
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13.Seybold D, Gessler U, Sigel A. Immunosuppressive therapy following kidney transplan­tation. Urologe A 1982;21:274-9.  Back to cited text no. 13
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14.Pedersen NC, Morris B. The role of the lym­phatic system in the rejection of homografts: a study of lymph from renal transplants. J Exp Med 1970;131:936-69.  Back to cited text no. 14
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15.Colvin RB. Emphatically Lymphatic. J Am Soc Nephrol 2004;15:827-9.  Back to cited text no. 15
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16.Lerut T, Lerut J, Broos P, Gruwez JA, Michielsen P. Lymphatic complications in renal transplan­tation. Eur Urol 1980;6:83-9.  Back to cited text no. 16
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17.Ebadzadeh MR, Tavakkoli M. Lymphocele After Kidney Transplantation, Where Are We Standing Now? Urol J 2008;5:144-8.  Back to cited text no. 17
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18.Halloren PF, Lui SL, Miller L. Review of transplantation. Clin Transpl 1996;9:10-3.  Back to cited text no. 18
    

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Correspondence Address:
Nariman Nezami
Clinical Pharmacy Laboratory, Drug Applied Research Center, Tabriz University (Medical Sciences), Tabriz, Eastern Azerbaijan
Iran
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DOI: 10.4103/1319-2442.98113

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