|Year : 2017 | Volume
| Issue : 3 | Page : 143-148
Declining trend of infections in renal transplant recipients in a tertiary care hospital from India
Sriram Sriperumbuduri, Karthik Kalidindi, Swarnalatha Guditi, Gangadhar Taduri
Department of Nephrology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, India
|Date of Web Publication||20-Dec-2017|
Dr. Karthik Kalidindi
Department of Nephrology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad - 500 082
Source of Support: None, Conflict of Interest: None
Introduction: Infections are an important cause of morbidity and mortality in renal transplant recipients. This retrospective study was done to study the infection profile in renal transplant recipients. Materials and Methods: Seventy-three patients who developed infections out of 144 renal transplant recipients at a tertiary care center in southern India between January 2010 and June 2014 were studied. Infections were analyzed in terms of incidence, time of onset after transplant, clinical presentation, diagnosis, graft dysfunction, and patient and graft survival. Results: A total of 145 infection episodes were documented in the 73 patients studied. Majority (79.5%) were males and females constituted 20.5%. Predominant age group involved was 21–30 years (38.4%). Most common donor was mother (30.1%). Induction therapy was given in 21 (28.8%) patients. Mean duration of follow-up was 21.3 months. Most common infections were those of urinary tract (34.5%), followed by viral (31.2%), sepsis (15.2%), mycobacterial (9.7%), and fungal (6.2%). Parasitic infections (giardiasis and Strongyloides hyperinfection syndrome) occurred in 2 (1.4%) patients. Cytomegalovirus accounted for 14.5% and BK virus for 5.5% of total infections. Majority (77.1%) of the infection episodes occurred in the first 6 months of transplantation. There were 11 (7.6%) episodes of graft dysfunction and three patients had graft failure. A total of nine deaths were recorded due to these infections. Conclusion: Urinary tract is the most common source of infection in renal transplant recipients, followed by viral infections. Understanding the chronologic pattern of these infectious episodes facilitates early diagnosis and management of patients.
Keywords: Anti-rejection therapy, diabetic status, infections, renal transplant recipients, risk factor profile
|How to cite this article:|
Sriperumbuduri S, Kalidindi K, Guditi S, Taduri G. Declining trend of infections in renal transplant recipients in a tertiary care hospital from India. Indian J Transplant 2017;11:143-8
|How to cite this URL:|
Sriperumbuduri S, Kalidindi K, Guditi S, Taduri G. Declining trend of infections in renal transplant recipients in a tertiary care hospital from India. Indian J Transplant [serial online] 2017 [cited 2020 Jun 3];11:143-8. Available from: http://www.ijtonline.in/text.asp?2017/11/3/143/221184
| Introduction|| |
Infections are an important complication in the posttransplant period and second common cause of death. Infections in a renal transplant patient are influenced by time duration after transplantation, immunosuppression protocols and dosage, anti-rejection therapy, and environmental factors. Development of a posttransplant timetable of infections by Rubin et al. has facilitated clinicians in differential diagnosis and a guide to design cost-effective targeted therapy and preventive strategies. Two more studies have been published from tropical countries which framed a timetable for posttransplant infections in this region., A similar attempt was made at our institute to prepare a timetable of infections, postrenal transplantation which may reflect the present trend of infections.
| Materials and Methods|| |
A retrospective analysis of all renal transplant recipients from January 2010 to July 2014 at Nizam's Institute of Medical Sciences, Hyderabad, India, was done. A total of 144 patients underwent renal transplant surgery in this period, which included living related and deceased donor recipients. Those who had at least one infection episode during their follow-up were included in the study. All patients were followed in transplant outpatient department as per institute protocol.
All patients were given methylprednisolone injection in a total dose of 3 g on the first 3 days, with triple immunosuppression that included tacrolimus (0.1 mg/kg/day routinely and if induction was given @ 0.08 mg/kg/day), mycophenolate mofetil (MMF) (600 mg/m 2/dose in two doses), and prednisolone 20 mg a day. Tacrolimus was tapered according to serum drug levels which were monitored on a monthly basis. Dose of steroid was tapered from 20 mg/day to 10 mg/day at the end of 6 months and continued thereafter. MMF was also tapered gradually in posttransplant period. Induction therapy was given in case of spousal or deceased donor transplantation with injection basiliximab (20 mg in two doses on day 0 and 4). Drug levels of tacrolimus were estimated on monthly basis and as and when required by liquid chromatography–mass spectrometry.
All patients receiving therapy for rejection and induction with basiliximab were given prophylaxis with oral valganciclovir, cotrimoxazole, and fluconazole for the next 3 months. All others were given prophylaxis with cotrimoxazole tablet for the first 6 months.
Patients were analyzed in every visit with blood urea, serum creatinine, and total leukocyte count. Monthly tests were done to analyze all the biochemical and hematological parameters along with viral parameters and cytomegalovirus (CMV) antibody screening. Any patient with suspected infection was evaluated thoroughly with investigations based on the clinical picture. Invasive tests were performed as and when required.
While analyzing infections, the following definitions were used:
- Urinary tract infection (UTI): Patients whose urine culture was positive for bacteria with colony counts >105 CFU/ml with symptoms of UTI
- Sepsis: Patients with systemic inflammatory response syndrome due to a presumed or proven bacterial etiology on blood culture (except UTI)
- Mycobacterial infections: Patients with organ-specific symptoms and/or signs and definite evidence of Mycobacterium tuberculosis growth on culture or positive acid-fast bacteria stain of fluids/sputum or positive polymerase chain reaction (PCR). Exudative serosal fluid with elevated adenosine deaminase levels – cutoff of 100 IU/l for pleural fluid and 90 IU/l for pericardial fluid was also taken as diagnostic of tuberculosis (TB)
- CMV infection or disease: Patients with clinical features of organ dysfunction (fever, cytopenias, diarrhea, etc.) and either positive anti-CMV IgM or CMV PCR or histologic evidence of disease (inclusion bodies of CMV) were diagnosed with CMV disease and those without organ involvement were diagnosed with CMV infection
- BK virus nephropathy (BKVN): Patients with positive blood BK virus PCR or graft biopsy suggestive of BKVN with or without graft dysfunction were included in this category
- Fungal infections: Patients with organ-specific symptoms and/or signs were diagnosed with cultures of blood, urine, and bronchoalveolar lavage or based on demonstration of fungal elements in tissue biopsies
- Parasitic infections: Patients with clinical symptoms and/or signs with diagnosis based on identification of ova in the stool and/or the presence of larval or adult forms in tissue specimen
- Herpes zoster and herpes labialis: These conditions were diagnosed based on clinical symptoms and signs with the presence of classical lesion – groups of vesicles on erythematous base
- Hepatitis C and hepatitis B: Patients with positive blood PCR for hepatitis C or B irrespective of symptoms or signs.
Graft dysfunction was defined according to AKIN staging- increase in serum creatinine of more than or equal to 0.3 mg/dl or increase to more than or equal to 150% to 200% from baseline.
Graft failure was defined as presence of irreversible graft dysfunction and requirement for RRT on a long-term basis.
| Results|| |
Out of 144 renal transplant recipients, 73 patients (50.7%) had 145 infection episodes. Males (79.5% - 58 patients) were predominantly affected than females (20.5% - 15 patients). Majority (38.4%) were in the age group of 21–30 years. Mean duration of follow-up was 21.3 months (1–43 months). Most common underlying renal disease was chronic glomerulonephritis seen in 48.6% patients, followed by chronic interstitial nephritis in 12.5% and diabetic nephropathy in 10.9%. Other causes included lupus nephritis, polycystic kidney disease, solitary kidney, and reflux nephropathy. Etiology was not known in 21.9%. Related donors (mother, father, sister, and brother) constituted 68.6% (50) and wife was the donor in 24.6% (18) cases. Deceased donor transplantation was done in 6.8% (five) patients. Induction therapy was given in 28.8% (21 patients). Rejection episodes were present in 32.9% (24 patients). New-onset diabetes after transplantation (NODAT) occurred in 21 patients. Preexisting diabetes was present in eight patients [Table 1].
|Table 1: Comparing the demographic data of patients who underwent renal transplantation during the time period from January 2010 to June 2014|
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Urinary tract infection was the most common infection accounting for 34.5% (50) of episodes followed by viral illness in 32.1% (46) of episodes. There were 22 (15.2%) episodes of sepsis and 14 (9.7%) of mycobacterial etiology. Fungal infections constituted 6.2% (9) of episodes and parasitic infections accounted for 1.4% (2) of episodes [Table 2].
|Table 2: Describing the total number and percentage of infections, mean time of onset (months after transplant), percentage with graft dysfunction, percentage requiring dialysis, and number of graft failure and deaths|
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| Discussion|| |
We have done a descriptive study of infections in renal transplant recipients from our institute in southern India. We analyzed the nature, etiology, pattern, and outcomes of these infectious episodes.
Similar to the previous studies,, the infection rate in our study was 50.7% (73 patients suffered infections out of 144 transplanted patients). The number of infection episodes was 145. The mean number of infectious episodes among patients who had at least one infection was 1.97 episodes per patient. This was less than that documented in a previous study  from our institute at 2.8 episodes per patient.
The infections in transplant recipients still follow the timetable which was published from our institute 10 years ago. We compared our time table with that from Rubin's study [Figure 1]. The immunosuppression protocol being followed changed from cyclosporine to tacrolimus and azathioprine to MMF. Despite this being a more potent immunosuppression than the previous one, infections rates were less. This shows the role of improved surgical theaters, postoperative wards, and chemoprophylaxis in reducing the posttransplant infections.
|Figure 1: Comparing the time table of infections in our study with Rubin's|
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The distribution pattern of infections revealed a clustering in the first 1 year with 126 (86.9%) of the episodes occurring in that period which corresponds with the period of intense immunosuppression. This is similar to another study from the Netherlands which had an incidence of 71%. About 25.5% (37 episodes) of the infections occurred in the 1st month, and by the 6th month, 77.9% (113 episodes) of infection episodes occurred [Figure 2].
The most common infection noted in our study was UTI which constituted 34.5% of the total episodes. This was identical with studies by Sousa et al. and Umesh et al. which reported 31% and 36.11%, respectively. However, previous study from our own institute reported very low frequency of UTI at 23%. Most (43%) of these infections occurred in the first 1 month. As with the previous study from our institute, the most common etiology was Escherichia More Details coli (54%), followed by Klebsiella (36%) [Table 3]. This is unlike the Western data which had shown a higher prevalence of Enterococcus.
|Table 3: Describing etiology of infections and diagnostic methods employed in each group|
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Among patients with UTI, double J stent was placed in 17 patients and 5 patients had no stent in situ.
The decision to place a double J stent in renal transplant patients was according to another study being done in urology department in the same time frame, and patients were randomized into two groups with stent being placed accordingly.
Viral infections constituted the second most common (32.1%) infection episode in our population. They included CMV, BKVN, herpes, and hepatitis. The incidence of varicella zoster was 7.6%, most of which presented with the involvement of multiple dermatomes, as seen with immunocompromised patients. A study from Brazil quoted an incidence of 9%.
CMV had an incidence of 14.5% in our study. This was similar to Umesh et al. study at 12.9%. The incidence has reduced in our institute compared to a previous study at 21.8%. The routine use of valganciclovir prophylaxis in all patients receiving induction therapy and following rejection for 3 months might have led to reduced CMV incidence. Seven patients had coexistent infections in the form of Klebsiella pneumoniae, sepsis with E. coli, localized abscesses (gluteal and suture site), parasitic infections such as Giardiasis, and Candida esophagitis. They probably represent the consequence of CMV-mediated immunosuppression which predisposed patients to other infections. Graft failure occurred in one patient with coexistent pulmonary TB. CMV pneumonia being one of the dreaded complications, led to death in one patient. One patient had acute cellular rejection episode within 3 weeks of CMV disease. Several studies have found an association between CMV and rejection episodes.,, Graft dysfunction was seen in 10% (two episodes). Five patients received valganciclovir prophylaxis and 16 did not receive any. More number of infections was present in people not receiving this prophylaxis though no statistical analysis was done due to small sample size.
BKVN had an incidence of 5.5%. Hirsch et al. reported BKVN incidence of 8%. The previous study from our institute  did not document any cases of BKVN. Immunosuppression used in that study population involved cyclosporine and azathioprine which had a lesser risk of this disease. The use of newer immunosuppressive combination (tacrolimus and MMF) and also the recent increase in awareness of this disease entity might have led to increased incidence in our study. The mean time of onset was 10 months in agreement with other studies which have shown onset at the same time frame of 11–13 months. Renal dysfunction was noted in one patient (12.5%), and it progressed to graft failure. Literature states a graft failure rate of up to 50% in BKVN.,, Prompt decrease in immunosuppression dose, involving withholding of MMF and decreasing the dose of tacrolimus along with the use of leflunomide, facilitated lower graft loss rates.
Sepsis was seen in 15.2% of episodes. This was similar to that reported in previous studies with rates of 6%–11%.,, Pulmonary infections due to bacterial etiology constituted 3.8% of episodes. This was much less compared to a study by Hoyo et al. that reported incidence rate of 8.8%.
The incidence of TB was 9.7%, including atypical mycobacterial infections. This was very much similar to that reported in Ram et al. and Umesh et al. at 11%. Although no deaths were recorded by these groups, case fatality was 20% in our series. Graft dysfunction was noted in 10%, which was less than that quoted by Ram et al. study at 38.5%. Invasive procedures such as bronchoscopy facilitated diagnosis in 3 of 7 patients with pulmonary TB, highlighting the importance of these procedures in workup of infections.
A special note is to be made about atypical mycobacterial infections in our study. Four cases were reported in the posttransplant period all of which responded to treatment with isoniazid, pyrazinamide, levofloxacin, and clarithromycin for 24 months. Few case reports exist of these pathogens in renal transplant patients.
Parasitic infections included two episodes, one each due to refractory giardiasis and Strongyloides hyperinfection syndrome. High degree of clinical suspicion with the use of invasive diagnostics in the form of colonoscopy and bronchoscopy made early diagnosis and good outcomes possible in both these infections.
The incidence of fungal infections in our study was 6.2%. The studies by Ram et al. and Umesh et al. quoted incidence of 9.5% and 16.62%, respectively. In our study, the most common causes were Candida species and Aspergillus in four patients each. A previous study from an institute from northern India reported similar etiology.
The chronologic pattern of infections described in this study is a useful entity during their evaluation in renal transplant recipients. It helps in clinical suspicion and targeted evaluation for etiology of infectious episode which, in turn, facilitates early diagnosis and management.
An attempt was made to compare a possible association of infections risk factors –diabetes (both pre existing and NODAT) and rejections. Although no statistical analysis could be made due to small sample size involved, more number of people with these risk factors had infections [Table 4].
|Table 4: Comparing the number of infections in patients with risk factors (induction, diabetes, and rejection) with those without risk factors|
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The drawback of our study was that a comparative analysis could not be made with the group of renal transplant recipients without any infectious episode due to small sample size of the latter-71. This might have helped in analyzing the possible risk factors for these infections. The protective effect of valganciclovir and fluconazole also could not be analyzed due to variable period of onset of these infections in patients taking these drugs. Although all the patients with reflux nephropathy had UTIs, it had no statistical significance when compared with patients of other etiology.
Despite using chemoprophylaxis, UTI predominates as the cause of infection. The role of indwelling catheter or double J stent as risk factors for this infection needs to be studied further. Regarding fungal and mycobacterial infections, exposure to environment and amount of immunosuppression played an important role. The development of CMV infection despite valganciclovir prophylaxis probably suggested interpatient variability in pharmacokinetics of immunosuppressive drugs. Individualizing the immunosuppression and monitoring and modulating their levels might help in decreasing the incidence of posttransplant infections.
| Conclusion|| |
This study described the pattern of infections in renal transplant recipients from a part of southern India in the era of modern immunosuppression. Infections tend to follow a chronological order, which helps in their early diagnosis. High degree of suspicion and invasive methods facilitates diagnosis of infections with rare etiology.
I would like to thank my colleagues and nursing staff who assisted us in our transplant work.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]