Saudi Journal of Kidney Diseases and Transplantation

BRIEF COMMUNICATION
Year
: 2019  |  Volume : 30  |  Issue : 1  |  Page : 151--152

Management and outcome of latent tuberculosis in living renal transplant donors


Wael T Habhab1, Basem M Alraddadi2, Naqi Idris1, Saeed Alghamdi1, Najla Zabani1, Ahmed Fahmy3, Ahmed Abdul Malik3, Mashael Alwaassia1,  
1 Department of Medicine, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia
2 Department of Medicine, King Faisal Specialist Hospital and Research Center; Department of Medicine, University of Jeddah, Jeddah, Saudi Arabia
3 Department of Surgery, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia

Correspondence Address:
Wael T Habhab
Department of Medicine, King Faisal Specialist Hospital and Research Center, P. O. Box: 40047, Jeddah 21499, MBC J 46
Saudi Arabia

Abstract

In regions where tuberculosis (TB) is endemic, up to 15% of kidney transplant recipients develop Mycobacterium tuberculosis infections (TBI), typically with an increased risk of disseminated disease and allograft loss. To reduce these risks, donors and recipients with latent TB usually receive isoniazid (INH) prophylaxis. However, it is unclear whether latent TB in donors justifies routine prophylaxis of recipients. At our institution, donors and recipients with latent infection receive INH prophylaxis, and those who do not have latent infections are not routinely treated. We retrospectively analyzed the records of 269 living donor kidney transplant recipient and donor pairs in order to determine the risk of posttransplant TB in those whose kidneys were obtained from living donors with latent TB. Three recipients (1.1%) developed active TB, three, 11, and 12 months after transplantation. Neither donors nor recipients in these pairs had evidence of latent TB before transplantation. Of the 224 pairs with complete data, 24 transplant recipients with negative tuberculin skin test received organs from living donors with evidence of latent TB. None developed active TB, and kidney function one and three years later was preserved. Our findings suggest that routine use of prophylaxis in recipients without latent TB who receive organs from positive donors might not add additional benefit.



How to cite this article:
Habhab WT, Alraddadi BM, Idris N, Alghamdi S, Zabani N, Fahmy A, Malik AA, Alwaassia M. Management and outcome of latent tuberculosis in living renal transplant donors.Saudi J Kidney Dis Transpl 2019;30:151-152


How to cite this URL:
Habhab WT, Alraddadi BM, Idris N, Alghamdi S, Zabani N, Fahmy A, Malik AA, Alwaassia M. Management and outcome of latent tuberculosis in living renal transplant donors. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2019 Jun 25 ];30:151-152
Available from: http://www.sjkdt.org/text.asp?2019/30/1/151/252905


Full Text



 Introduction



Posttransplant opportunistic infections continue to contribute significantly to both morbidity and mortality in kidney and other solid organ transplant (SOT) recipients.[1],[2],[3],[4] Mycobacterium tuberculosis infections (TBI) in kidney transplant recipients are frequently encountered in regions where tuberculosis (TB) is endemic; the incidence of posttransplant TBI in endemic areas may reach 15%, whereas the reported incidence in most European and North American transplant centers ranges from 0%–6.5%.[4],[5] Up to one-third of postrenal transplant patients with TBI develop disseminated disease, and the overall mortality is as high as 30%.[6],[7]

For pretransplant recipients with positive tuberculin skin tests (TST) and latent TBI (LTBI), several randomized trials and meta-analyses have demonstrated the effectiveness of prophylactic treatment with isoniazid (INH) prophylaxis,[8],[9],[10],[11] although the reported degree of efficacy for preventing posttransplant TBI varies.[8] Rifampin prophylaxis showed similar results; however, both drugs may cause potentially severe hepatotoxicity.[12] Rifampin risks also include significant adverse effects on posttransplant immunosuppression, resulting in allograft injury or loss.[10],[11],[12]

Opinions vary about whether LTBI in donors confer a significant risk of TBI in TST-negative transplant recipients. Such a risk could justify prophylaxis in this group of transplant patients. This is a key issue given the mortality risk associated with posttransplant TBI and the more frequent episodes of rejection, chronic allograft nephropathy, and diminished allo-graft survival rates.[3],[9],[13] Several large series have shown that the majority of posttrans-plant TB cases result from the underlying LTBI in recipients;[14],[15],[16] pre and posttransplantation prophylaxis of these recipients diminishes the risk of M. tuberculosis reactivation.[17],[18],[19] The evidence supporting TBI in recipients resulting from the transfer of M. tuberculosis from LTBI donor kidneys is less clear;[3],[20] few of the reported cases provide convincing evidence to implicate the donor kidney as the likely source of recipient infection.[21]

We conducted a retrospective study of living donor/recipient renal transplant pairs from Saudi Arabia in a region where TB is endemic,[22] to determine the risk of TBI following transplantation of kidneys from donors with LTBI into TST-negative recipients.

 Materials and Methods



Study patients

Medical records of all kidney transplantations performed at the King Faisal Specialist Hospital and Research Center, Jeddah Branch, between 2002 and 2012, were retrospectively reviewed in order to select patients whose kidneys were from living donors.

Living donor transplant cases were excluded if there was no recorded screening history for TB exposure and prior TBI, allograft loss or recipient death occurred within the first 30 posttransplant days, or an active TBI was present at the time of the transplant. Transplant TST for both recipients and donors was considered positive if there was induration of at least 10 mm measured at 48–72 h.

The diagnosis of active TBI before or after transplantation was based on clinical symptoms that included fever, weight loss, and malaise plus either a chest X-ray with typical active TBI findings or the identification of M. tuberculosis in a cultured clinical specimen. A latent TBI was defined as a positive TST with no clinical indicators of an active infection. All living donors and recipients with LTBI received INH prophylaxis with a daily dose of 5 mg/kg up to a maximum of 300 mg beginning at least two weeks before transplantation. All donors completed their prophylaxis for a total of nine months after donating the organ.

Recipients' prophylaxis continued for an additional nine months following the transplant. Recipients without LTBI received no prophylaxis regardless of the donor LTBI status. At our institution, postrenal transplant immuno-suppression consists of steroids, tacrolimus, and mycophenolate.

Clinical data

Information collected for donor/recipient pairs included age at the time of transplant, gender, date of transplant, history of TBI, TB exposure, prior TB treatment, diabetes mellitus (DM), the dates and results of pre-transplant TSTs, and any prior prophylaxis or treatment for a TBI.

Additional data collected from recipient records included clinical episodes of active TBI occurring during the 1st posttransplant year, serum creatinine results for the first three posttransplant years, the type of induction therapy if administered, the number of rejection episodes, graft loss and date, and patient morbidity or mortality and cause.

This study was approved by Institutional Review Board of the King Faisal Specialist Hospital and Research Center-Jeddah Branch.

 Statistical Analysis



Data were analyzed using Statistical Package for the Social Sciences software version 20 (IBM Corporation, Armonk, NY, USA). Data were described using mean, median, and interquartile range for continuous variables and frequencies and percentages for categorical variables. Chi-square test and Fisher's exact test, where appropriate, were used to compare dichotomous variables. t-test was used to compare continuous variables.

 Results



During the period of review, a total of 269 living donor transplants (47.2% male) were performed at our center and met our inclusion criteria [Figure 1]. The median age of transplant recipients was 38.5 years. DM was the underlying cause of end-stage renal disease in 58 recipients (21.9%). Antithymocyte globulin was used for induction in 92 patients (34.2%), basiliximab was used in 113 (42%), and 64 (23.8%) received no induction.{Figure 1}

Pretransplant TST was positive in 31 (13.8%) and 39 (17.4%) of donors and recipients, respectively. Of the 31 transplant recipients who received kidneys from donors with positive TST, 24 (10.7%) were TST negative [Table 1].{Table 1}

Three patients developed active TBI at 3, 11, and 12 months after transplant, with an incidence of 1.1% [Table 2]. All cases had microbiological confirmation. In all the three episodes, both donors and recipients were TST negative and had no prior history of TBI. None of the three recipients developed rejection during the 12 months following transplantation. Median serum creatinine at 12 and 36 months posttransplant were not significantly different compared to the remainder of the cohort [77.7 μg/L (0.88 mg/dL) and 87.3 μg/L (0.99 mg/ dL), respectively, in the transplant group vs. 90 μg/L (1.02 mg/dL) and 88 μg/L (1.0 mg/dL), respectively, in the general cohort].{Table 2}

 Discussion



In this study of 269 living donor–recipient pairs, the incidence of TBI was 1.1% after kidney transplantation. This incidence is higher when compared to that of the general population in the region and is consistent with previous observations in other endemic regions.[1],[23],[24],[25]

While several studies have implicated recipient LTBI reactivation as the most common cause of posttransplant TBI,[6],[26] the infections in our patients were most likely community acquired because both the donors and recipients in these cases had negative TST, and no history of prior TBI or treatment.

The adverse effects of TBI on graft and patient survival, as well as the potential toxicity of TB treatment regimens, have particular importance in endemic regions. Disseminated TB occurs in up to 30–35% of cases and an additional 15–30% of the infections are extrapulmonary.[7],[23],[25] Mortality attributed to TBI occurs in as many as 25–35% of cases,[6],[26],[27] and more than one-half develop chronic rejection.[28] Furthermore, treatment-associated hepatotoxicity has been observed in about one-third of recipients developing active TBI; one-half of these cases were severe.[17] Thus, posttransplant active TB infections are associated with a higher risk of patient death, allograft dysfunction or loss, and treatment-associated hepatotoxicity. Clearly, active post-transplant TBI has serious and potentially life-threatening consequences, and interventions to prevent posttransplant TBIs appear to be justified.

The prevention of posttransplantation de novo TBI can be particularly challenging in TB-endemic localities. Agarwal et al conducted a randomized controlled study of TBI prevention using INH prophylaxis beginning on the day of transplant for all recipients. Their results included a favorable but statistically insignificant trend of prevention of TBI with prophylaxis.[9] Of note in that study, INH-induced hepatitis occurred in only one of the thirty treated patients, although greater risks of hepatitis have been reported by others.[10] For transplant candidates with LTBI, the use of INH prophylaxis prior and subsequent to transplantation has become a common practice. Investigations of INH prophylaxis as a preventive measure for TBI reactivation have shown variable results, although most randomized studies and meta-analyses suggest varying degrees of effectiveness.[8],[9],[29],[30] However, there is currently no consensus about patient selection for prophylaxis, and reported treatment regimens vary considerably.[31]

The benefit of donor prophylaxis is more controversial, and current data are scant. There have been several reports of cases in which transmission of TBI from the donor kidney is very plausible.[21],[32] However, this phenomenon appears to be quite rare and for the majority of the reported cases, the evidence was equivocal. [21] There are also very little published data on the outcomes of donor prophylaxis, although a study of donor INH prophylaxis from Mexico, where TB is endemic, found no benefit from INH prophylaxis in donors with LTBI.[20] Our study included 31 kidneys from donors with LTBI, all of whom received INH prophylaxis. Of these, 24 (77%) were transplanted into LTBI-negative recipients; none had received INH prophylaxis and none developed TBI. Our findings suggest that the risk of posttransplant TBI acquired from the donor kidney is rare, and that INH prophylaxis of LTBI-negative recipients in this setting provides no additional benefit.

Our study is subject to several limitations. First, as a retrospective study, some of the important data were missing, in particular, the duration of pretransplant INH prophylaxis. Second, recipients with negative pretransplant TST results did not undergo repeat testing, and it is possible that some of the donors (and recipients) who initially had negative TST would have subsequently become positive as a result of the “booster” effect.[33],[34] Third, there is no available data regarding the BCG vaccination in our study population; however, very small effects of BCG on TST reactions are expected after 10 years for people vaccinated in infancy.

In conclusion, we did not observe cases of posttransplant TBI that were attributable to LTBI in the donors. Our data suggest that INH prophylaxis for transplant recipients with negative TST from positive donors might not add an additional benefit. Future prospective studies are needed to confirm this finding.

Conflict of interest:

None declared.

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