Objectives: Renal transplant is one of the best ways to extend life of patients in the end stage of renal disease. Infections are significant causes of morbidity and mortality after renal transplant. The aim of this study was to evaluate frequency, risk factors, causative pathogens, and clinical manifestations in renal transplant recipients from Mashhad City during the first year after transplant.

Materials and Methods: This research was conducted at Montaserie Hospital of Mashhad University of Medical Sciences from March 2013 to July 2015. All studied cases were followed for 1 year. In this retrospective study, our study cohort comprised 193 kidney trans­plant recipients, including 118 male (61.1%) and 75 female (38.9%) patients, with mean age of 34.4 ± 12.2 years. Of the total patients, 58 received kidneys from living donors (30.1%) and 135 received kidneys from deceased donors (69.9%).

Results: We found that 151 infectious episodes had occurred in 96 patients. The most common infectious site involved the urinary tract (39.1%). Escherichia coli was the most frequently isolated pathogen. The only significant infection risk factor to affect transplant outcomes during the first year was age.

Conclusions: Infections are highly prevalent during the first year after transplant. Prevention and effective antibiotic therapy can reduce the related adverse effects.

Key words : Kidney transplantation, Urinary tract infection

Introduction

Renal transplant is one of the best ways to extend life for patients with end-stage renal disease.^1,2 Renal allograft survival rates are 95% for transplants from living donors and 89% for transplants from deceased donors during the first year after transplant.³ There are 2 important problems that can affect a successful renal transplant: the first one is allograft rejection and the second is serious infections.⁴ Choosing suitable prophylaxis and immunosuppressive drugs can provide a safer outcome for renal transplant reci­pients.

In the past, acute rejection was a primary reason for patient hospitalization posttransplant. Currently, hospitalization due to infections is more of a concern than rejection during the first year after transplant.⁵ Studies have indicated that the most important causes of death after transplant are cardio­vascular disease, infection and cancers.⁶ The incidence of infectious complications after renal allograft trans­plant has ranged from 49% to 80%.⁷ The risk of post-transplant infection depends on immunosuppressive therapies, epidemiologic exposures, and invasive and surgical procedures.^2,8 Immunosuppressive treatment is a common cause of infections in renal transplant recipients.⁹

The most serious infections happen during the first 6 months after transplant due to a more intensive immunosuppressive regimen. Once im­munosuppressive therapies are reduced, chronic, occasional opportunistic, and general community-acquired infections often occur.^1,6

Because information is lacking regarding pre­sence of risk factors, frequency, causative pathogens, and clinical profiles of renal transplant recipients during the first year after renal transplant in the northeast of Iran, this study was performed to evaluate these parameters.

Materials and Methods

This retrospective study was conducted at the Mashhad University of Medical Sciences and was approved by the University’s ethics committee. For this research, we investigated medical records of all patients who underwent renal transplant procedures at the University’s Montaserie Hospital. This research involved patients seen from March 2013 to July 2015, and patients were followed for 1 year. Patients who did not live in Mashhad and who had incomplete records were excluded from this research. All patients had received intraoperative double J stents. Transplant procedures were conducted using standard techniques.

Standard immunosuppressive therapy for all patients included prednisolone, cyclosporine, or tacrolimus. Other drugs included ceftriaxone for surgical prophylaxis, isoniazid for donor or recipient with positive tuberculosis skin test, and methyl prednisolone with or without rabbit antithymocyte globulin for antirejection treatment. Antimicrobial prophylactics involved nystatin and cotrimoxazole against Pneumocystis jiroveci and candida. Ceftriaxone was used for all patients; none of patients received any prophylactic agents against Cytomegalovirus (CMV).

Presence of fever or any signs of infection was confirmed by clinical laboratory diagnosis test. Infections were classified according to time after transplant, causative pathogen, and site of infection.

Sites and diagnosis of infections
The site of infection was classified based on definitions from the US Centers for Disease Control and Prevention as mentioned below¹⁰ and included the following sites: urinary, intra-abdominal, wound infection, respiratory, mucocutaneous, primary bacteremia, vulvovaginitis, and intravascular.

Urinary tract infections (UTI) were identified by positive urine culture (> 100,000 colony-forming units/mL) and/or febrile conditions. Any clinical symptoms of UTI such as frequency, urgency, dysuria, suprapubic pain, and hematuria were confirmed by laboratory examination.

Intra-abdominal infections, such as peritonitis, cholangitis, abdominal abscess formation, and pan­creatitis were assessed by physicians’ examination.

Regarding wounds, presence of a purulent secretion from a surgical incision confirmed by culture was identified as a wound infection. Fungal infections were recognized by strong proof of tissue invasion from histologic examination or detection in blood or other sterile sites.

Respiratory tract infections were diagnosed by dyspnea, chest discomfort, and fever. This condition was validated by radiologic examination or positive culture of BAL (Brancheal Alveolar Lavage).

Bacteremia was diagnosed by presence of fever, chills, or hypotension. It was confirmed by pathogen grown in blood culture.

Cytomegalovirus disease was defined by fever, myalgia, malaise, arthralgia, leukopenia, throm­bocytopenia, and organ-specific manifestations. This infection was confirmed by the detection of CMV DNA in blood samples, using real-time polymerase chain reaction assay. The diagnosis of labial herpes simplex infection, genital herpes infection, and varicella zoster infection were based on appearance of unilateral vesicular lesions and confirmed by a dermatologist. The available diagnostic test for BK virus infection was viral load assessment in urine sample.

Serum creatinine levels were measured to identify effects of infection on transplant outcomes. We analyzed the incidence of infectious episodes according to sex, age, cause of end-stage renal disease, and creatinine levels at the time of infection occurrence.

Statistical analyses
Statistical analyses were performed with SPSS software (SPSS: An IBM Company, version 18, IBM Corporation, Armonk, NY, USA). P < .05 was considered statistically significant. According to data distribution, suitable statistical tests were applied.

Results

We reviewed the medical records of 193 patients who underwent renal transplant from March 2013 to July 2015 at the Renal Transplant Unit of Montaserie Hospital in Mashhad City. Demographic charac­teristics of patients are summarized in Table 1.

The youngest and the oldest studied patients were 6 years and 66 years old. We found that 58 patients received grafts from living donors, with 29 (50%) having infections. There were 135 patients with grafts from deceased donors, with 67 (49.62%) developing infections.

During the study period, 151 infectious episodes were recorded in 96 of 193 patients (49.7%), with mean of 0.8 episodes per recipient and 1.5 per infected patient. In addition, in the 151 infectious episodes in 96 patients, 61 patients (63.5%) had 1 episode, 22 patients (22.9%) had 2 episodes, 7 patients (7.3%) had 3 episodes, 5 patients (5.2%) had 4 episodes, and 1 patient (1%) had 5 infectious episodes. The common infections and the time of occurrences are presented in Table 2.

Average serum creatinine level was 1.75 ± 1.01 mg/dL at first incidence, 1.96 ± 0.99 mg/dL at second incidence, and 2.26 ± 1.63 mg/dL at third incidence of infection. As shown in Table 1, the only significant infection risk factor affecting transplant outcome during the first year was age (odds ratio 1.132; P = .006).

All infectious causes and number of episodes are listed in Table 3. The most common infection was UTI (59 episodes, 39%). Two UTI patients were infected concomitantly by 2 different pathogens. The most common pathogens overall were Escherichia coli, Klebsiella, and Staphylococcus. At least 1 episode of viral infection occurred in 57 of 151 infectious episodes.

Discussion

Cardiovascular disease, infection, and cancer are the most frequent causes of death during the early posttransplant period.⁶ Recently, the prevalence of infections has declined due to improvements in surgical techniques and immunosuppressive medi­cations, as well as improvements in prophylaxis.¹¹ With standard immunosuppression treatment regimens, the incidence of posttransplant infections has been reported to range from 49% to 81%, as indicated previously.^7,12 Infectious complications after kidney transplant are associated with significant morbidity.¹³ Posttransplant infection incidence and patterns may vary due to different social, environmental, and financial conditions among countries.¹⁴ In this study, we assessed infection and related factors in renal transplant patients in Mashhad City, Iran.

During the first few days after transplant, urethral catheters are used for surgical anastomosis pro­tection, and these may be a potential risk factor for UTIs.8 Incidence of UTIs has been reported to range from 6% to 86% in transplant patients, with the most common type being bacterial infections.^15,16 In our patients, the main isolated bacteria found in cultures included Escherichia coli, Klebsiella, and Staphylococcus. In our study, UTI was one of the most common complications after transplant, with incidence rate of 39.1%.

Incidence of respiratory infections has been shown to range from 2.5% to 16% in renal transplant patients.¹⁷ Our results demonstrated respiratory tract infection in 5 patients (3.3%). Other studies have reported infections with Pneumocystis jiroveci in 1.6% to 11.5% of patients.^8,18 However, none of our patients were affected by Pneumocystis jiroveci, which may be due to the appropriate use of prophylaxis.

In our study, wound infections occurred in 2.6% of all infected recipients, which is a lower incidence than that shown in similar studies. Other studies have shown a rate of wound infection of 4% to 10.3%.^1,17 Intra-abdominal infection constituted 2% of overall infections in our study, compared with a reported incidence in the literature of 4% to 7%.¹ It seems that surgical technique improvement, better wound management, and prophylactic agents have resulted in reduced infection rates.

In contrast with other studies, tuberculosis was not observed. In developing countries, mycobacterial infections are one of the life-threating infectious diseases. Its incidence rate varies widely, from less than 1% in the United States to 11% to 15% in India.^17,19 In the same study,¹⁷ Iran had a reported incidence of tuberculosis of 1.4% and median duration between transplant and tuberculosis occurrence of 21 months.¹⁴ It seems that the short follow-up of patients in our study may explain the absence of tuberculosis. More follow-up may be needed to better determine rates of tuberculosis infection.

Bacteremia incidence was 7.3% in a study from Pourmand and associates, with E. coli being the most prevalent isolated pathogen in that study.²⁰ These results are comparable with our present findings.

Viral infections were found in 35% of infected patients, and these were more frequent in the first 3 months after transplant. In addition, 29.1% of infectious episodes were attributed to CMV. Other studies have revealed that CMV infection occurs in 6% to 80% of renal transplant patients.^7,21 In our center, none of the transplant recipients received prophylactic agents against CMV, which may have caused the high incidence of this virus. Infectious episodes may trigger allograft rejection and reactivate latent CMV infection.²² The prevalences of herpes simplex virus and varicella zoster virus infections in kidney transplant recipients have been reported to be 7% to 53% and 12%.²³ In this study, incidences were 3.3% and 3.9%. A recent study demonstrated the incidence rate of herpes zoster to be 1.6% by the end of the first year after kidney transplant.²⁴

The occurrence of fungal infections after kidney transplant was 0.87% in Iran and ranged from 1.4% to 6.9% in other countries.²⁵ Fungal infections constituted 9.2% of the overall pathogens in our research. Candida albicans was the most common microorganism during this time, which colonizes in mucosa routinely and may lead to superficial mucositis, such as cystitis or esophagitis.

Conclusions

In this series of patients, the higher the age of the kidney transplant recipient the higher the risk of infection. Despite advances in posttransplant prophylaxis, prevalence of bacterial infections has stayed constant in the past decade. Removal of urethral catheter as soon as possible has been advised to reduce risks of infections. The prevention of CMV infection with prophylaxis is an important matter. This study confirmed that infections remain a serious problem in kidney transplant recipients. These patients must be assessed and followed with more care. We also recommend treatment of every infection before transplant.

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