Saudi Journal of Kidney Diseases and Transplantation

CASE REPORT
Year
: 2012  |  Volume : 23  |  Issue : 5  |  Page : 1017--1023

Tuberculosis of the arterio-venous graft in a renal transplant recipient


Fakhriya Alalawi, Amna Alhadari, MJ Railey, Mona Alrukhaimi 
 Department of Nephrology, Dubai Hospital, Dubai Health Authority, Dubai, United Arab Emirates

Correspondence Address:
Fakhriya Alalawi
Department of Nephrology, Dubai Hospital, Dubai Health Authority, Dubai
United Arab Emirates

Abstract

A 44-year-old Pakistani lady with end-stage renal disease secondary to rapidly proliferative glomerulonephritis underwent successful renal transplantation. Three years later, she was referred to the surgeon with an abscess in the axillary region at the site of a previous arterio-venous (AV) graft. She underwent repeated incision and drainage of the abscess, which was constantly recurring. Nine months later, she presented with a tender swelling at the site of the AV graft with purulent discharge. The graft was removed; culture and histology confirmed the presence of tuberculosis (TB). This patient presents a rare case of TB infection in the AV graft.



How to cite this article:
Alalawi F, Alhadari A, Railey M J, Alrukhaimi M. Tuberculosis of the arterio-venous graft in a renal transplant recipient.Saudi J Kidney Dis Transpl 2012;23:1017-1023


How to cite this URL:
Alalawi F, Alhadari A, Railey M J, Alrukhaimi M. Tuberculosis of the arterio-venous graft in a renal transplant recipient. Saudi J Kidney Dis Transpl [serial online] 2012 [cited 2022 Jan 21 ];23:1017-1023
Available from: https://www.sjkdt.org/text.asp?2012/23/5/1017/100884


Full Text

 Introduction



Tuberculosis (TB) is a common disease world­wide; the World Health Organization had ack­nowledged TB as a global emergency in 1993. [1] Epidemiologists had estimated that one-third of the world population is infected with tubercu­lous bacilli, which accounts for nearly eight to ten million new cases of TB and three million deaths annually throughout the world. [2]

The risk of acquiring the disease is increased in immunosuppressed individuals, including pa­tients on dialysis and recipients of kidney trans-plants. [3] The site and clinical manifestations may be atypical and diagnosis often delayed thus re­sulting in high morbidity and mortality. [4],[5]

A case of a renal transplant recipient with TB infecting the AV graft is reported here with review of the literature.

 Case Report



A 44-year-old Pakistani lady presented in March 2003 with history of generalized weak­ness, lower limb edema and puffiness of the face of four days duration. She gave a history of recurrent right loin pain for three months pre­ceding her presentation; she denied any past history of joint pain or skin rash.

Her laboratory tests showed severe renal failure with a serum creatinine (SeCr) of 8.1 mg/dL and urinalysis showed 18-20 white blood cells and numerous red blood cells; urine culture was negative. Ultrasound of the abdomen showed slightly enlarged kidneys, with the right kidney measuring 12.3 cm and the left kidney measu­ring 13 cm; the cortico-medullary differentiation was well preserved.

A clinical diagnosis of rapidly progressive glomerulonephritis was made and after optimizing her chemistry with hemodialysis (HD), she un­derwent a kidney biopsy, which was reported as diffuse crescentic glomerulonephritis. She received three doses of pulse methylprednisolone followed by oral prednisolone. She also re­ceived three doses of cyclophosphamide infu­sion at intervals of four weeks. The last dose of cyclophosphamide was given in June 2003.

Her kidney functions were reassessed; however, she remained dialysis dependent (creatinine clearance 8 mL/min). A left arterio-venous (AV) Gore-Tex graft between the axillary vein and the brachial artery was created in June 2003 with primary failure. She continued to have dia­lysis via a right internal jugular catheter.

In November 2003, she underwent renal trans­plantation in Pakistan from a live unrelated donor. Details pertaining to her pre-transplant assessment were not available. However, her post-operative course was uneventful and she was maintained on azathioprine and cyclosporine along with steroids. On return to Dubai, she was regularly followed-up in the transplant cli­nic; she maintained good graft function and the serum creatinine ranged between 0.9 mg/dL and 1.2 mg/dL.

In January 2006, the patient was referred to the surgeon for abscess in the left axillary region. She underwent incision and drainage on multiple occasions due to poor wound healing and recurrent sinus formation. Repeated wound cultures did not grow any organisms.

On September 11 2006, she was admitted with painful left upper arm swelling of 15 days dura­tion associated with low-grade fever. There was no history of weight loss or past or family history of tuberculosis (TB). Clinical examina­tion revealed a tender swelling at the site of the AV graft with purulent discharge. A diagnosis of cellulitis with infected graft was made and the patient was treated empirically with flucloxacillin. Wound and blood cultures did not grow any organisms.

The severely infected graft was removed sur­gically in September 2006; histology of the skin, underlying soft tissue and lymph node showed necrotizing caseating granulomatous inflammation with sinustract formation, abscess forma­tion and fibrosis. Special staining for acid fast bacilli (AFB) Ziel Nielson as well as staining for fungi (Periodic Acid Shciff and Grcott Methanamine Silver) was negative. One focus showed a foreign body giant cell reaction to keratin flakes, suggesting the possibility of a ruptured keratinous cyst. The presence of caseating nec­rosis with epithelioid granulomas was consis­tent with TB [Figure 1]. The lymph node also showed granulomatous lymphadenitis, although her chest X-ray was normal [Figure 2].{Figure 1}{Figure 2}

Culture from the purulent discharge was re­ported to be positive for AFB after eight days of incubation; thus, the patient was confirmed to have TB of the AV graft. She was started on triple drug anti-TB therapy [pyrazinamide, isoniazid (INH) and rifampicin], with the aim to continue INH and rifampicin for a total of six months, and give pyrazinamide for the initial two months only.

During her follow-up in the clinic, her wound had healed completely, her SeCr ranged between 0.9 and 1 mg/dL, but the cyclosporine level remained persistently low despite an increase incyclosporine dosage (cyclosporine trough level ranged between 45 and 88 ng/mL on repeated occasions).

She remained with us for nearly six weeks after starting anti-TB treatment, after which she was lost to follow-up till March 2007. When she reappeared, her serum creatinine had increased from 1 to 2.6 mg/dL and the cyclosporine trough level was 43 ng/mL. The patient claimed that she was very compliant with her medications and that no change had been made in her immunosuppressive drugs. Urine examination was normal and she was treated as acute rejection, keeping in picture the persistent low cyclosporine level. She received pulse methyl prednisolone for three days (at that time, she had com­pleted seven months of anti-TB medication), despite which the serum creatinine increased further to 3 mg/dL. Allograft sonography showed pelvicalyceal dilatation at the upper end of the ureter with no evidence of calculus formation. This was confirmed on computerized tomogra­phy scan, following which she was seen by the urologist who inserted a nephrostomy tube, des­pite which the serum creatinine failed to de­cline. The creatinine levels were fluctuating bet­ween 3 and 4 mg/dL, with an estimated glomerular filtration rate (GFR) of 18 mL/min. An antegrade nephrostogram was performed, which revealed free flow of the injected contrast into the urinary bladder with no significant obs­truction. However, multiple kinks were seen along the ureter, together with fullness of the pelvicalyceal system, suggestive of partial obs­truction or a reflux [Figure 3]. She was ob­served with the nephrostomy tube in situ for nearly five weeks till May 2007 with no change in her chemistry; she was eventually recom­menced on HD in October 2007.{Figure 3}

 Discussion



The incidence of infection with Mycobacterium TB in patients on HD and renal transplant recipients is high in developing countries. [3] Incidence rates of ten to 25 cases per 100,000 per year have been reported from the United States, Canada, Europe, Middle East, India, South Asia and Japan, which accounts for 10-25-folds greater risk than those in the general population. [3],[6],[7],[8],[9],[10],[11],[12]

This increase is attributed to multiple and com­plex immunological factors associated with end­stage renal disease (ESRD), [13] which result in a change in the immune status, both cellular and humoral. [14],[15],[16] The lymphocytes in uremic pa­tients are reduced in number and have sup­pressed mitogenic response. [14],[16] There is also a reduction in the phagocytic activity of the polymorphonuclear leukocytes. [17] Thus, uremic pa­tients are unable to produce a high titer of anti­bodies in response to infection. [14] Other factors include disturbance of cytokine network, [13],[18] enhanced release of TNFα[17] and presence of circulating immune complexes, which can in­fluence the immune response of dialysis patients. [15],[18] Descamps et al have described the presence of advanced oxidation protein pro­ducts in the plasma of uremic patients, which can act as both potential uremic toxins and proinflammatory mediators. [19] Immunosuppressive drugs pose an additional risk in renal transplant recipients. [20],[21]

The incidence of TB in transplant recipients varies according to geographical distribution; usually it ranges between 0.35 and 4% in most of the world. [3],[22],[23],[24],[25],[26] However, in India, Sakhuja et al had reported a high incidence of 11.8%, of whom 58.3% were diagnosed within one year of transplant. [12] The epidemiological distribution of TB in a country is an important risk for the development of TB after transplantation. [5]

The diagnosis of TB may be complicated in patients with ESRD because they often have atypical clinical presentation, negative skin tests, non-specific symptoms that may be attributable to uremia and a higher occurrence of extra-pulmonary TB (accounts for 25-40%), compared with other patient populations. [5],[7],[20],[22],[25],[27],[28],[29],[30] Dia­betes mellitus [3],[10],[26],[31] and chronic liver disease [26] have been observed to be common diseases associated with TB.

Lungs and pleura are the most favored sites for TB, [3],[4],[5],[10],[20],[26],[30] although it can occur in various other organ systems of the body. [20] There are many reported cases of rare sites of extra-pul­monary TB; tuberculous bacilli were isolated from laryngeal biopsy and smear in two renal transplant recipients in India who had pre­sented with prolonged hoarseness of voice and odynophagia, [20] while a young lady in Saudi Arabia was reported to have pulmonary TB with supraglottic mass causing suffocation 1.7 years after transplant. [32] The other rare forms of TB reported include TB of the glans penis, [33] TB causing multiple skin ulcers, [26] skin TB from a nodule of the right breast, [34] tuberculous liver abscess, [35] TB of the small bowel presenting as fecal peritonitis [30] and bone marrow TB with severe pancytopenia causing a rare syndrome (hemophagocytic syndrome) with infiltration of bone marrow by extensive necrotizing granulomas. [36],[37],[38] This extra-pulmonary presentation in unusual sites may result in a delay in the diag­nosis, thereby increasing the morbidity and mortality of immunocompromised individuals.

Cutaneous TB is an unusual presentation in renal transplant recipients; [39] it can present with recurrent abscesses or a picture indistingui­shable from cellulitis, [26] which is probably the scenario in our case, who presented with recur­rent axillary abscess and later as cellulitis of the AV graft limb. It might be that the AV graft acted as a nidus that can attract inoculation of different organisms, including TB. The mycobacteria could be typical or atypical; a short duration of growth supports atypical ones.

In most of the published reports, cyclosporine was found to be associated with increased risk of TB in renal transplant recipients within six years of transplant [12],[26] (in our case she had developed TB at three years post-transplant). This is attributed to cyclosporine-induced inhi­bition of proliferation of lymphocytes and mac­rophages. Recent reports suggest that mycophenolate and tacrolimus are more potent than cyclosporine and azathioprine in inducing TB in the early transplant period. [6]

The treatment of TB in renal transplant reci­pients is controversial and the optimum dura­tion of anti-TB therapy is not well defined. In some centers, treatment is given for a minimum period of one year, [39],[40] while others extend it for 18 months. [12],[20] However, most physicians still feel that a short course of anti-TB drugs (six to nine months) is effective in all forms of TB, especially in those living in non-endemic areas. [28],[29],[41],[42] Treatment is based on an initial two-month intensive phase in which, usually, four drugs including rifampicin, isoniazid, pyrazinamide and ethambutol are given, [40] and these destroy almost all tubercle bacilli. This is followed by a continuation phase in which only rifampicin and isoniazid are given.

Rifampicin increases the rate of metabolism of a wide range of drugs, including corticosteroids, cyclosporine and tacrolimus. Regular measure­ment of blood concentrations of cyclosporine and tacrolimus in such patients is recommended. [6],[11],[12] Chronic allograft nephropathy is very common in renal transplant recipients on rifampicin, [43],[44] probably as a result of interaction between rifampicin and cyclosporine. [21] Some centers have tried to eliminate rifampicin from anti-TB regimens to avoid the high cost of immunosuppressive therapy, and they have reported good success. [1],[3],[8],[12],[31]

Close watch has to be kept in all renal trans­plant recipients for recurrence of TB after dis­continuation of chemotherapy, as clinical fea­tures may be vague because of immunosuppression. The role of isoniazid prophylaxis in renal transplant recipients is still debatable. [45],[46]

Infection of a dialysis AV graft should be treated with appropriate therapy; complete graft excision is required in most cases to ensure a favorable outcome and reduced mortality rate. [47],[48]

Our patient had dilated pelvicalyceal system requiring nephrostomy; she might have had ureteric involvement as part of TB leading to urinary tract obstruction and/or reflux. If uri­nary tract TB is suspected, relief of obstruction by stenting or percutaneous nephrostomy may aid functional recovery, especially in patients with good renal cortical thickness, limited renal involvement and a GFR more than 15 mL/min. [28] However, in our case, nephrostomy could not delay the progression to graft failure.

There are only two published reports in the world of TB affecting a vascular graft; one in 1977, where Wright et al had reported Mycobacterium tuberculosis in a prosthetic aortic graft (Dacron) placed in a patient to treat aortoiliac occlusive disease, and the second report in 2004 by Raffetto et al of aortobifemoral Dacron graft bypass done to treat Takayasu arteritis. [48] However, to the best of our knowledge, our case is the first published report of TB affecting dialysis AV graft in a renal transplant recipient.

 Acknowledgments



The authors would like to thank the histopathology department in Dubai Hospital for their contribution of the histology microphotographs and the radiology department for their contribution of the X-rays film.

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