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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 18  |  Issue : 4  |  Page : 112-115

Risk factors, clinical manifestations, and outcomes of Pneumocystis jirovecii infection in post-renal transplant recipients


Department of Nephrology, Mahatma Gandhi Hospital, Jaipur, India

Date of Submission10-Oct-2018
Date of Acceptance30-Oct-2018
Date of Web Publication17-Dec-2018

Correspondence Address:
Dr. Jitesh Jeswani
Senior Resident in Nephrology Mahatma Gandhi Hospital, Jaipur - 302022
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jesnt.jesnt_30_18

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  Abstract 


Introduction Pneumocystis jirovecii pneumonia (PJP) is a potentially life-threatening infection that occurs in immunocompromised patients. A timely diagnosis of PJP is difficult and relies on clinical features, imaging, and detection of the organism. The aim of this study was to evaluate the risk factors, clinical presentation, and outcomes for 15 patients who developed PJP infection.
Patients and methods A retrospective clinical study included all 578 kidney transplant patients who underwent kidney transplantation at the Mahatma Gandhi Medical College and Hospital, Jaipur, Rajasthan. Of the 578 patients, 15 patients developed PJP infection.
Results The median age of all recipients was 55.3 years. The mean duration of prophylaxis was 6.9 months (range: 3–9 months). Only one patient had cytomegalovirus infection, and eight patients had a history of graft rejection. Most of our patients had fever and cough as the presenting symptoms, and all patients had breathlessness on admission. Bilateral haziness seen on chest radiograph was present in seven patients, and 10 patients had bilateral ground-glass appearance on high-resolution computed tomography scan. PCR finding for PJP was positive in all patients. Mortality was seen in four patients, where all the four cases had received anti-rejection therapy with ATG.
Conclusion We concluded that among renal transplant recipients, PJP can still occur several months after transplantation, late after prophylaxis discontinuation. Treatment with anti-rejection therapy appears to be the major risk factor for PJP in these patients.

Keywords: graft rejection, immunocompromised, Pneumocystis jirovecii pneumonia, renal transplant


How to cite this article:
Jeswani J, Godara S, Bhagat C. Risk factors, clinical manifestations, and outcomes of Pneumocystis jirovecii infection in post-renal transplant recipients. J Egypt Soc Nephrol Transplant 2018;18:112-5

How to cite this URL:
Jeswani J, Godara S, Bhagat C. Risk factors, clinical manifestations, and outcomes of Pneumocystis jirovecii infection in post-renal transplant recipients. J Egypt Soc Nephrol Transplant [serial online] 2018 [cited 2019 Jan 20];18:112-5. Available from: http://www.jesnt.eg.net/text.asp?2018/18/4/112/247708




  Introduction Top


Pneumocystis jirovecii pneumonia (PJP) formerly known as Pneumocystis carinii pneumonia is a potentially life-threatening infection in immunocompromised patients [1],[2]. In patients who are not on prophylaxis, PJP occurs in ∼5–15% of transplant patients, depending on the transplanted organ [2],[3]. In renal transplantation, PJP is a very serious risk factor for graft rejection and patient mortality [4],[5]. In the absence of appropriate cure, the mortality rate of PJP is 90–100% and can be as high as 50% despite adequate therapy [6],[7].

Risk factors for the development of PJP in kidney transplant patients are high doses of immunosuppressive therapy, higher donor age, higher recipient age, lymphopenia, previous cytomegalovirus (CMV) infection, or treatment used for episodes of graft rejection [8],[9]. However, factors identified in some studies are not always confirmed in other studies. The aim of this study was to evaluate the risk factors, clinical manifestations, and outcomes of PJP in kidney transplantation recipients.


  Patients and methods Top


A retrospective clinical study included all kidney transplant patients who underwent kidney transplantation at the Mahatma Gandhi Medical College and Hospital, Jaipur, Rajasthan, from May 2013 to September 2018. During this period, 578 patients underwent kidney transplantation, of which, 15 patients who were suspected on clinical and radiological grounds were diagnosed to have PJP infection. In our center, all kidney transplant recipients receive PJP prophylaxis using trimethoprim/sulfamethoxazole (TMP/SMX) 160/800 mg on alternate days for 12 months after transplantation; hence, none of the patients in our study group were on prophylaxis when they were diagnosed with PJP infection. After transplantation, patients received steroid plus tacrolimus plus mycophenolate mofetil combination regimen for maintaining immunosuppression.

Clinical data on demographic characteristics, immunosuppressive regimen, history of graft dysfunction, history of CMV, biochemical parameters, and clinical outcomes were evaluated.


  Discussion Top


PJP is an opportunistic infection that occurs in 6% of RTRs if no prophylaxis is given. In our study, of 578 kidney transplant patients, 15 patients developed PJP. Risk of PJP infection was higher in patients who had history of rejection or received ATG. When acute graft rejection occurs, patients are treated with steroid pulse therapy or other immunosuppressive agents. These results support the hypothesis that severe immunosuppression may increase the occurrence of PJP. Similarly, low lymphocyte counts have been reported to be associated with the development of PJP [10].

Lufft et al. [11] first reported that different immunosuppressive regimens could affect the occurrence of PJP in renal transplant recipients. In their report, tacrolimus-based regimens seemed more likely to trigger PJP; all patients in our study group were on combination of steroid plus tacrolimus plus mycophenolate mofetil. The US Renal Data System cohort showed no association between induction immunosuppression levels and PJP risk but did show that regimens containing sirolimus were associated with PJP infection [12]. None of our cases were on sirolimus.

The median time from transplant to the development of disease was 36 months in our study. The timing of PJP infection in post-transplant patients depends upon the duration of prophylaxis and the hike in immunosuppression during anti-rejection therapy. Our patients had wide variation in time of presentation. One patient who was diagnosed with PJP infection at 3 months after transplant was stopped TMP-SMX after transplant in view of persistent hyperkalemia. The recommended duration of PJP prophylaxis is 6–12 months after solid organ transplantation [13]. The Kidney Disease: Improving Global Outcomes clinical practice guidelines recommend 3–6 months of post-transplant prophylaxis, and at least 6 weeks during and after treatment for acute rejection [14]. The European Best Practice guidelines recommend at least 4 months of prophylaxis after transplant, with a further 3–4 months of prophylaxis during rejection [15].

Our study showed that significant PTH-independent hypercalcaemia (corrected calcium>10.7 mg/dl) was observed. The reason for this has been postulated in the past owing to increased hydroxylation via 25-hydroxyvitamin D 1-α hydroxylase from alveolar macrophages leading to hypercalcaemia [16].

Mean value of LDH observed in our study was 355.0 U/l which is an indirect marker of PJP infection. All patients were confirmed with PJP infection by Pneumocystis PCR done on bronchoalveolar lavage samples or sputum. Most of our patients had fever and cough as the presenting symptom, and all patients had breathlessness on admission.

Bilateral haziness seen on chest radiograph was present in seven, and 10 patients had bilateral ground-glass appearance on high-resolution computed tomography (CT) scan; PCR finding for PJP was positive in all patients (bronchoalveolar lavage or Sputum sample).

Hence, a high index of suspicion, good microbiological support, and early bronchoscopy with high-resolution CT of the chest are cornerstones to pick up cases early.

Mortality was seen in four patients which can be attributed to the delayed presentation of patient to the hospital, more immunocompromised state as all of these patients had received anti-rejection therapy with ATG, and elderly age.


  Results Top


Demographic and clinical characteristics of the total study population are presented in [Table 1]. Overall, 578 patients were enrolled over the 4-year study period. The median age of all recipients was 55.3 years (range: 32–60 years). Four patients died of 15 patients; all of whom were above 50 years of age, which showed that older age had poor disease prognosis.
Table 1 Characteristics and outcome of 15 cases of Pneumocystis jirovecii pneumonia among renal transplant recipients

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Most cases developed infection 3–36 months after kidney transplantation. One patient who was diagnosed with PJP infection at 3 months after transplant was stopped TMP-SMX after transplant in view of persistent hyperkalemia. Only one patient had history of CMV infection, and over half of the cases (8/15) patients had history of receiving ATG for anti-graft rejection therapy.

In clinical presentation, fever was present in 80% of cases, and mean duration of fever was 4.8 days; cough was present in 10 patients; and all patients (N=15) had respiratory distress. SPO2 on presentation was 88.1% (mean) at room air, and average pulse rate was 112.7/min. Moreover, 12 of 15 patients had respiratory signs demonstrable in the form of crackles or wheeze.In biochemical parameters, mean value of lactate dehydrogenase (LDH) was 355.0, mean corrected calcium was 10.71 mg%, PTH was 33.9 mmol/l, and graft dysfunction was observed in nine out of 15 cases, with average serum creatinine being 2.63 mg/dl in our study.

Radiographically, bilateral haziness seen on chest radiograph was present in seven patients and 10 patients had bilateral ground-glass appearance on high-resolution CT scan. PCR finding for PJP was positive in all patients (bronchoalveolar lavage or sputum sample) ([Table 2]).
Table 2 Correlation between outcome and duration of transplant and prophylaxis

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All patients diagnosed with PJP were started on TMP/SMX-15 mg/kg adjusted for GFR of the patient. Eight patients required second-line medication because of disease progression despite TMP-SMX use; they were treated with primaquine and clindamycin, of which 50% patients did not survive.

Eleven patients with PJP improved after treatment, and all required noninvasive ventilation; four patients received both first-line and second-line drug therapy for PJP. However, four patients died, all requiring invasive ventilation and first-line plus second-line therapy for PJP ([Table 1]).


  Conclusion Top


Among renal transplant recipients, PJP can still occur several months after transplantation, late after prophylaxis discontinuation. Graft rejection appears to be the major risk factor for PJP in these patients. Elevated LDH and corrected calcium are indirect markers of PJP infection. Early recognition and cohort prophylaxis for 12 months is a proven strategy that can limit PJP progression, with a multidisciplinary approach representing a crucial component in preventing PJP infection.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Thomas CF, Limper AH. Pneumocystis pneumonia. N Engl J Med 2004; 350:2487–2498.  Back to cited text no. 1
    
2.
Sepkowitz KA, Brown AE, Armstrong D. Pneumocystis carinii pneumonia without acquired immunodeficiency syndrome. More patients, same risk. Arch Intern Med 1995; 155:1125–1128.  Back to cited text no. 2
    
3.
Radisic M, Lattes R, Chapman JF, del Carmen Rial M, Guardia O, Seu F et al. Risk factors for Pneumocystis carinii pneumonia in kidney transplant recipients: a case–control study. Transpl Infect Dis 2003; 5:84–93.  Back to cited text no. 3
    
4.
Coyle PV, McCaughey C, Nager A, McKenna J, O’Neill H, Feeney SA et al. Rising incidence of Pneumocystis jirovecii pneumonia suggests iatrogenic exposure of immune-compromised patients may be becoming a significant problem. J Med Microbiol 2012; 61:1009–1015.  Back to cited text no. 4
    
5.
Gordon SM, LaRosa SP, Kalmadi S, Arroliga AC, Avery RK, Truesdell-LaRosa L et al. Should prophylaxis for Pneumocystis carinii pneumonia in solid organ transplant recipients ever be discontinued? Clin Infect Dis 1999; 28:240–246.  Back to cited text no. 5
    
6.
Festic E, Gajic O, Limper AH, Aksamit TR. Acute respiratory failure due to Pneumocystis pneumonia in patients without human immunodeficiency virus infection: outcome and associated features. Chest 2005; 128:573–579.  Back to cited text no. 6
    
7.
Sepkowitz KA. Opportunistic infections in patients with and patients without acquired immunodeficiency syndrome. Clin Infect Dis 2002; 34:1098–1107.  Back to cited text no. 7
    
8.
Arichi N, Kishikawa H, Mitsui Y, Kato T, Nishimura K, Tachikawa R et al. Cluster outbreak of Pneumocystis pneumonia among kidney transplant patients within a single center. Transplant Proc 2009; 41:170–172.  Back to cited text no. 8
    
9.
De Boer MG, Kroon FP, le Cessie S, de Fijter JW, van Dissel JT. Risk factors for Pneumocystis jirovecii pneumonia in kidney transplant recipients and appraisal of strategies for selective use of chemoprophylaxis. Transpl Infect Dis 2011; 13:559–569.  Back to cited text no. 9
    
10.
Struijk GH, Gijsen AF, Yong SL, Zwinderman AH, Geerlings SE, Lettinga KD et al. Risk of Pneumocystis jiroveci pneumonia in patients long after renal transplantation. Nephrol Dial Transplant 2011; 26:3391–3398.  Back to cited text no. 10
    
11.
Lufft V, Kliem V, Behrend M, Pichlmayr R, Koch KM, Brunkhorst R. Incidence of Pneumocystis carinii pneumonia after renal transplantation. Impact of immunosuppression. Transplantation 1996; 62:421–423.  Back to cited text no. 11
    
12.
Neff RT, Jindal RM, Yoo DY, Hurst FP, Agodoa LY, Abbott KC. Analysis of USRDS: incidence and risk factors for Pneumocystis jiroveci pneumonia. Transplantation 2009; 88:135–141.  Back to cited text no. 12
    
13.
Chapman JR, Marriott DJ, Chen SC, MacDonald PS. Post-transplant Pneumocystis jirovecii pneumonia − a re-emerged public health problem? Kidney Int 2013; 84:240–243.  Back to cited text no. 13
    
14.
Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant 2009; 9(Suppl 3):S1–S155.  Back to cited text no. 14
    
15.
EBPG Expert Group on Renal Transplantation. European best practice guidelines for renal transplantation. Section IV: long-term management of the transplant recipient. IV.7.1 Late infections. Pneumocystis carinii pneumonia. Nephrol Dial Transplant 2002; 17(Suppl 4):36–39.  Back to cited text no. 15
    
16.
Reichel H, Koeffler HP, Barbers R, Norman AW. Regulation of 1,25-dihydroxyvitamin D3 production by cultured alveolar macrophages from normal human donors and from patients with pulmonary sarcoidosis. J Clin Endocrinol Metab 1987; 65:1201–1209.  Back to cited text no. 16
    



 
 
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