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Infectious Disease Complications of Renal Transplantation at the University

of the East Ramon Magsaysay Memorial Medical Center (UERMMMC)1

Sue-Ann R. Locnen, M.D.2, Adrian C. Pena, M.D.3, Yvonne Abrihan-Arce, M.D.2 and Ma.

Cyrille U.Cerezo, M.D.4

(1 From the Department of Medicine, University of the East Ramon Magsaysay Memorial Medical Center(UERMMMC), Aurora Boulevard, Quezon City, Philippines. 2 Resident, Department of Medicine, UERMMMC.3 Associate Professor and Chief, Section of Infectious Diseases, Department of Medicine, UERMMMC.

4Fellow,

Section of Nephrology, Department of Medicine, UERMMMC.)

ABSTRACT

A retrospective review of infections in renal transplant recipients at the UERMMMC from January 1997 to

April 1999 was done. The nature of the infectious disease complication, site and time of occurrence in relation totransplantation was noted. There were 28 renal transplant procedures during the study period but only 25 (89.29%)

patients had available hospital and outpatient records for review. A total of 28 episodes of infection were noted. Themost common type is urinary tract infection (UTI), 64.3%) followed by Pneumonia (17.85%). The most common site

of infection is the urinary tract (64.3%) followed by the lower respiratory tract (21.42%). Bacterial infections weremost common (82.14%). Three episodes of fungal infections (10.7%) and two episodes of viral infections (7.14%) were

documented. Throughout the post-transplant period, UTI was the most prevalent type of infection. Regardless of thetype, most infections occurred between the 1st and 6th month post-transplant (60.7%). One patient died of infectious

complication from multiple pathogens. The present study underscores the significance of infection in the care of thetransplant recipient. It also confirms that UTI remains the most common infection in the post-transplant periodespecially during the 1st 6 months and infections from multiple pathogens are rapidly fatal. (Phil J Microbiol Infect Dis2000; 29(3):119-122)

Key words:post-transplant infections, renal transplantation, pneumonia, urinary tract infection

INTRODUCTION

Since the dawn of the age of transplantation, infectious diseases continue to beset renal

transplant recipients. Although the incidence and severity of infectious complications are on a

downward trend, prevention and treatment remain major concerns among transplant patients.

Two major factors affect the risk of infection among transplant patients: first is the

epidemiological exposure to infective agents and second is the net immunosuppressive effect

present.

Epidemiologic exposure happens either in the community or in the hospital. Hospital-

acquired infections may be domiciliary or non-domiciliary. The former happens in the hospital

unit where the patient is confined while the latter occurs during transport within the hospital as a

result of exposure to contaminated air.1 The net state of immunosuppression is the sum of several

factors including the nature of immunosuppressive therapy, presence of underlying immune

deficiency, metabolic conditions and infections with immunomodulating viruses like

Cytomegalovirus (CMV). Immunosuppression is indeed a main risk factor for infection in

transplant recipients.1-2

The timetable of infections after transplantation is typically divided into three parts: the

1st month post-transplant, 1st to 6th month post-transplant and the late period covering beyond 6months of transplantation. Infections in the 1st month after transplantation are mostly the same

nosocomial bacterial and candidal wound infections, post-operative pneumonia and catheter

related infections present in the regular surgical patient without immunosuppression. From the 1st

to the 6th month post-transplant, new types of infections appear in addition to the residual effects

of previous episodes. The immunomodulating viruses such as the CMV and Epstein-Barr virus

(EBV) begin to be present clinically, making possible the occurrence of opportunistic infections

even if no excessive exposure to opportunistic pathogens is present. In the late post-transplant

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period, recipients who enjoy good results from transplantation are maintained with minimum

imrnunosuppressive agents. The infections experienced by these patients are not different from

those present in the general community such as influenza and pneumococcal pneumonia.

However, there is a subset of patients who will have chronic and progressive viral infections

acquired earlier like chronic hepatitis. Finally, in those who suffer recurrent or chronic rejection,

opportunistic infections are always a threat due to the need for irnmunosuppression.1

The purpose of this study is to determine the types, onset, sites and outcome of infectionsin patients who underwent renal transplantation at the UERMMMC.

MATERIALS AND METHODS

This is a retrospective study of infectious disease complications in patients who

underwent renal transplantation at the UERMMMC from January 1997 to April 1999.

Charts of patients were reviewed and the onset, types and sites of infections were noted.Outcome of treatment was also noted. The temporal sequence of infections post-transplantation

were grouped into: 1st month, 1st to 6th month and beyond 6 months.

Infections were diagnosed according to standards or when the attending physician

diagnoses and treats a presumed infection. Means and percentages (frequencies) were used in the

analysis of data.

RESULTS

A total of 28 renal transplants wore done during the study period. Only the records of 25

(89.28%) were available. Among 25 patients, 20 (80%) were males and 5 (20%) were females

with a mean age of 43.2 (range: 21-70 years). The most common etiology of end stage renal

disease (ESRD) was chronic glomerulonephritis (Table 1).

Table 1. Age, sex and underlying renal ailment of renal transplant patients.

Characteristics Number (%)

Age 21-70 years

(ave. =43.2)Sex MaleFemale

205

(80%)(20%)

Etiology of ESRD

Chronic glomerulonephritisDM nephropathyIgA nephropathyPolycystic kidney disease

Chronic pyelonephritisObstructive UropathyHypertensive nephrosclerosisUnknown

11622

1111

442488

4444

Total 25 100

A total of 28 episodes of infections were noted in 18 of the 25 patients (Table 2). Themost common type was urinary tract infection (64.3%)occurring between 31 to 180 days post

transplant (64.7%). At any time after transplantation, the urinary tract was the most common site

of infection (64.3%) as seen in Table 3.

The next most common type of infection was pneumonia (17.85%), all occurring during

the 1st 6 months after the transplant procedure. The respiratory tract was likewise the next most

common site (21.42%). All lower respiratory tract infections were pneumonias except 1 episode

of pulmonary aspergillosis occurring 241 days post-transplant. The remaining types of infections

demonstrate single episodes each (3.57%) of systemic cytomegalovirus infection, varicella,

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orbital mucormycosis and pharyngeal candidiasis, all occurring 31 to 180 days post-

transplantation.

Table 2. Type and timing of occurrence of infections post-transplantation

Type of infection Timing (days)

1-30 31-180 >180 Total

n (%) n (%) n (%) n (%)

UTI 5 (62.5) 11 (64.72) 2 (67) 18 (64.3)Pneumonia 3 (37.5) 2 (11.76) 5 (17.85)CMV 1 (5.88) 1 (3.57)

Varicella 1 (5.88) 1 (3.57)Mucormycosis 1 (5.88) 1 (3.57)Aspergillosis 1 (33) 1 (3.57)Candidiasis 1 (5.88) 1 (3.57)

Total 8 (100) 17 (100) 3 (100) 28 (100)

Table 3. Site and timing of occurrence of infections post-transplantation.

Site of infection Timing (days)

1-30 31-180 >180 Total

n (%) n (%) n (%) n (%)Urinary tract 5 (62.5) 11 (64) 2 (67) 18 (64.3)Respiratory tract 3 (37.5) 2 (12) 1 (33) 6 (21.42)Eye 1 (6) 1 (3.57)Throat 1 (6) 1 (3.57)

Systemic 1 (6) 1 (3.57)Skin 1 (6) 1 (3.57)

Total 8 (100) 17 (100) 3 (100) 28 (100)

Table 4. Type of pathogen and timing of occurrence of infection post-transplantation.

Pathogen Timing (days)

1-30 31-180 >180 Total

n (%) n (%) n (%) n (%)

Bacterial 8 (100) 13 (76.47) 2 (67) 23 (82.15)Viral 2 (11.76) 2 (7.14)Fungal 2 (11.76) 1 (33) 3 (10.71)

Total 8 (100) 17 (100) 3 (100) 28 (100)

The majority of infections were bacterial in etiology 82.14% as seen in Table 4. Although

not all the UTI's were cultured, all were presumed bacterial and were treated as such. Five of the

LRTI's were treated as bacterial. In one patient with LRTI,Aspergillus sp. was documented in thesputum culture.

There were only 2 episodes of viral infections both occurring 1 to 6 months after

transplantation. The first is systemic CMV proven by serology and the other is Varicella

diagnosed clinically. There were 3 cases (10.7%) of fungal infections - one patient had both

orbital mucormycosis and pharyngeal candidiasis proven by culture.

Of the 25 patients included in the study, 1 died 58 days post-transplant. The patient hadmultiple types of infection - complicated UTI, pneumonia, systemic CMV, pharyngeal

candidiasis and orbital mucormycosis. All the other infections resolved after medical treatment

including hospitalization when necessary.

DISCUSSION

This study shows that infection remains a significant cause of morbidity and mortality in

renal transplant recipients. Following the typical temporal profile of post-transplantation

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infections, the present study is compatible with previous reports in that infections are most

common during the 1st 6 months post-transplant.1,2,3 However, this conclusion is unlike that of a

local study wherein the percentage of infections were almost equal during and after the 1st 4

months post-transplant.4

The urinary tract is the most common site of infection, a result which is consistent with

both local and foreign studies.1,2,5,6 Although UTI in the first 6 months post-transplant is

frequently associated with overt pyelonephritis, only one patient in this study developed suchillness 54 days post-transplant. In contrast, UTI occurring after 6 months has a relatively benign

course.5Like other studies, pneumonia is noted to be the next most common type of infection.

Also, it is universally known to be the most common infectious cause of mortality in renal

transplant recipients. This was not proven in the present study because the single mortality died of

multiple infections. In the first month post-transplant, bacterial pneumonia predominated but in

the late post-transplant period, both conventional and opportunistic infections may occur.5-6As in the previous studies, bacterial infections remain to be the most common. Instead of

viral infections, the next most common infection noted is fungal in etiology. Although fungal

infections were believed to occur much later in the post-transplant period, opportunistic infections

are still known to occur earlier especially when sustained immunosuppression is combined with

immunomodulating viral infections. In the patient who died, the CMV infection may have causedfurther immunosuppression thereby making opportunistic infections possible.1

The nature of infection relative to the time of occurrence post-transplant likewise

changes. Of note is the finding that only UTI and pneumonia are the type of infections during the

1st month. This changed during the 2nd to 6th month post-transplantation wherein other types of

infection set in. This finding is consistent with those found by Fishman. 1 Six months after

transplantation, patients who were maintained on minimal immunosuppression experienced the

same type of infections as those found in the general community. But patients who are in

recurrent rejection or those who harbor chronic viral infections may be susceptible to

opportunistic infections. The pulmonary aspergillosis noted in this study was diagnosed in a

patient who was experiencing the former condition.

The present study shows that inspite of the advancement in transplantation and the

decreasing trend in infectious diseases, these complications still contribute significantly to themorbidity in renal transplant recipients. It is therefore important that they be recognized early and

treated properly.

RECOMMENDATIONS

The importance in diagnosing infectious disease complications in transplant recipients

can never be overemphasized. Thus, it is recommended that a prospective study be made on

future transplant patients of the institution. All suspected infections should be documented by

serology and culture studies so that clinicians may be guided properly and accordingly.

REFERENCES

1. Fishman JA, Rubin RH. Infection in organ transplant recipients. N Eng J Med 1998; 338(24):1741-1751.2. Sia IG, Paya CV. Infectious complications following renal transplantation. Surg Clin North Am 1998; 78(1):95-

113.

3. Mendoza MT, Liquette RR, Ona ET, Alano FA. Infections in renal allograft patients: A review of the Philippineexperience. Int J Infect Dis 1997; 1(4):222-225.

4. Dumo CC, Pena AC, Chua JA, Licuanan KG, Veloso MH, Dalay CV. Infections in renal transplant recipients atthe St. Luke's Medical Center. Phil J Intern Med 1999; 37(2):87-91.

5. Rubin RH, Wolfson JS, Cosimi AB, Tolkoff-Rubin NE. Infection in the renal transplant recipient. Am J Med

1981; 70:405-411.6. Peterson P, Andersen R. Infection in renal transplant recipients. Am J Med 1986; 81:2-10.