44 J Contemp Med Sci | Vol. 8, No. 1, January-February 2022: 44–46 Original A study of the Incidence of Cytomegalovirus Infection and Preemptive Therapy in Kidney Transplant Recipients Zana Sidiq Mohammed Saleem1*, Kais H Abd2, Nashwan M.R. Ibrahim3, Nawfal R Hussein4, Hasanain MA Al-Khammas5 1Department of Internal Medicine, College of Medicine, University of Duhok, Duhok, Iraq. 2Duhok Renal Dialysis and Organ Transplant Center, Duhok, Kurdistan Region, Iraq. 3Department of Surgery, College of Medicine, University of Duhok, Duhok, Iraq. 4Department of Medicine, College of Medicine, University of Zakho, Zakho, Kurdistan Region, Iraq. 5Basrah Center for Kidney Disease and Renal Transplant Center, Ministry of Health, Basrah, Iraq. *Correspondence to: Zana Sidiq Mohammed Saleem (E-mail: zanasidik@gmail.com) (Submitted: 13 December 2021 – Revised version received: 28 December 2021 – Accepted: 07 January 2022 – Published online: 26 February 2022) Abstract Objectives: This study aimed to determine the incidence of CVM infection and evaluate the outcome of preemptive treatment. Methods: This prospective, two centers cohort study included recipients who underwent renal transplant between May 2019–May 2020. The incidence of CMV infection and graft outcomes were studied. All managed with preemptive therapy. Results: In this study, 134 renal transplant recipients were recruited. Among them, 30/134 (22.4%) patients tested positive for CMV-RTPCR. We studied the impact of age on the CMV-positivity and we found that the age of the doner was associated with CMV-positivity (P = 0.025; OR = 0.923; CI = 0.8584–0.9943). Smoking and gender showed no association with CMV-positivity. Conclusion: Our data suggest that the course of CMV infection is benign with a high success rate of preemptive treatment. Further evaluation for the universal prophylactic plan is needed. Keywords: CMV, preemptive, Iraq, kidney, transplant ISSN 2413-0516 Introduction CMV causes asymptomatic diseases in immunocompetent patients and it does not need specific treatment. However, it can cause serious diseases that lead to deleterious outcomes in pregnancy and immunocompromised patients such as AIDS patients and organ transplant recipients.1-3 In organ transplant recipients including renal transplant, CMV infec- tions are the major cause of infectious diseases morbidity and mortality with an incidence ranging from 19–90%.4 To pre- vent organ rejection, organ transplant recipients are markedly immunosuppressed in the first three months after the opera- tion.4 This gives the opportunity for CMV to infect different organs including colon and retina.4 Without prophylaxis or preemptive treatment, such an infection may lead to three outcomes: infectious disease syndrome; increased immuno- suppression or organ rejection.4,5 Ganciclovir and valganci- clovir are the first-line medications for prophylaxis and treatment of such infections.5 The chance of CMV infection after organ transplant is determined by the status of donor and recipient CMV serology. To prevent infections in high- risk patients (D+/R–), prophylactic medications can be given, whereas preemptive strategy can be used for moderate risk (D+/R+, D–/R+) or low risk patients (D–/R–).4-6 Such a plan of CMV treatment and prevention is not used in some trans- plant centers due to economic burden and medications una- vailability. This may lead to an increased rate of CMV infections and high rates of CMV resistance and relapse.1,3,6 Post-transplant infection has been studied thoroughly in our center.7-10 In our organ transplant center, prophylactic strategy was not used due to the expense and unavailability of the medications. The aims of this project were to determine the incidence of CVM infection and evaluate the outcome of preemptive treatment. Materials and Methods Study Design This was a prospective cohort study that was conducted in Duhok and Basrah organ transplant centers between May 2019–May 2020. Patients In the study period, all renal transplant recipients were recruited in the study. In our center, all renal transplant recip- ients were managed according to the local protocol and the immunosuppressant regimen was composed of anti- thymocyte globuline (ATG) 1.5 – 2 mg/Kg at operation day and 4th day after the operation, tacrolimus 0.075 – 0.15 mg/Kg, Mycophenolate 2 g/day) and prednisolone (1 mg/kg/day then titrate to maintenance 7.5 mg/day). All renal transplant recip- ients were followed up in the centers. All recruited subjects were asked to visit the center monthly. In each visit, 5 CC blood was collected from the patients. Serum was separated and was kept frozen at –20˚C until CMV RTPCR was per- formed. No CMV prophylaxis was given to patients. Patients were tested on a monthly basis for CMV-RTPCR positivity. We followed up patients for 6 months after transplant. During the follow up, we evaluated the incidence of CMV infection, the efficacy of ganciclovir and valganciclovir, graft survival or failure. Serum creatinine and blood urea were used as indica- tors for graft functionality. CMV RTPCR and IgM/IgG CMV RTPCR was performed utilizing artus CMV RG PCR kit (Hilden, Germany) following the instructions of the manu- facturer. The amplification was performed using a rotor gene real time PCR system from Qiagen (Hilden, Germany). mailto:zanasidik@gmail.com 45J Contemp Med Sci | Vol. 8, No. 1, January-February 2022: 44–46 Z.S. Mohammed Saleem et al. Original A study of the Incidence of Cytomegalovirus Infection and Preemptive Therapy The patients were followed up monthly for three successive months after transplant. To determine CMV status, Elecsys CMV IgM and Elecsys CMV IgG kits were utilized (COBAS, Roche, Mannheim, Germany). Ethics This study was approved by the Ethics Committee in the Col- lege of Medicine, University of Zakho. Written consent was obtained from all recruited patients. Statistics Binary logistic regression was utilized to study the relationship between clinical outcomes and factors. All calculations were performed using Minitab 17 software. Results Patients In this study, 134 renal transplant recipients were recruited. 69.4% of them were male and the mean age of our patients was 39 ± 13.3 years (Table 1). All donations came from living donors; cadaver donation was not acceptable religiously and socially. CMV serology study showed that all recipients and donors were CMV IgG positive/IgM negative. RTPCR Positive Patients During the follow up period, 30/134 (22.4%) patients tested positive for CMV-RTPCR. Among those, 18 (60%) were male and the average age of 39.97 ± 12.48 (Table 2). CMV-positive patients gave the history of hemodialysis of 9.8 ± 19 months (Table 2). The infection did not affect the function of the graft. We studied factors that might impact CMV-positivity in renal transplant recipients (Table 3). We studied the impact of different diseases prior to the transplant such as hypertension, diabetes, glomerulonephritis or renal stone. We found no association between those diseases and CMV positivity. Then, we studied the impact of age on the CMV-positivity and we found that the age of the doner was associated with CMV-pos- itivity (P = 0.025; OR = 0.923; CI = 0.8584 – 0.9943) (Table 3). Smoking and gender showed no association with CMV- positivity (Table 3). CMV-RTPCR became negative within a Table 1. Characteristics of recipients Characteristics No % Gender M 93 69.40 HT 108 80.60 DM 26 19.40 APCKD 7 5.22 GN 12 8.96 Stone 2 1.49 Others 25 18.66 Age (mean ± ST) 39 ± 13.3 HD (mean ± ST) 6.88 ± 11.4 Table 2. Characteristics of post-transplant CMV positive Characteristics No % Sex (male) 18 60 HT 25 83.3 DM 6 20 GN 3 10 Stone 1 3.3 Other 5 16.7 APCKD 0 0 Age 39.97 ± 12.48 HD 9.8 ± 19 Table 3. Difference between post-transplant CMV positive and negatives Factors CMV Negative CMV Positive P OR CI95 Age R 38.75 ± 13.5 39.97 ± 12.48 0.66 1.01 0.9764–1.0385 Age D 29 ± 6.51 26.17 ± 5.99 0.025 0.923 0.8584–0.9943 Sex (male) R 75/104 (72.11%) 18/30 (60%) 0.2 0.58 0.2487–1.3528 Sex (male) D 70/104 (67.3%) 19/30 (63.33%) 0.68 0.83 0.3593–1.9591 HD 6 ± 7.9 9.8 ± 19 0.131 1.02 0.9927–1.0581 HT 83/104 (79.8%) 25/30 (83.33%) 0.663 1.26 0.4327–3.6989 DM 20/104 (19.23%) 6/30 (20%) 0.925 1.05 0.3791–2.9086 GN 9/104 (8.65%) 3/30 (10%) 0.822 1.17 0.2966–4.6377 Stone 1/104 (0.96%) 1/30 (3.33%) 0.39 3.55 0.2155–58.5392 Other 20/104 (19.23%) 5/30 (16.67%) 0.75 0.84 0.2861–2.4659 Smoking 74/104 (71.15%) 22/30 (73.33%) 0.82 1.11 0.4471–2.7798 APCKD 7/104 (6.73%) 0 1 0 0 month of the treatment in 25/30 (83.33%) patients. By the end of the second month, all patients tested negative for CMV-RTPCR. Discussion Post-transplant CMV prophylaxis can reduce the risk of infec- tion during the early stage after transplant operation. How- ever, there is a concern about late onset infection after the 46 J Contemp Med Sci | Vol. 8, No. 1, January-February 2022: 44–46 A study of the Incidence of Cytomegalovirus Infection and Preemptive Therapy Original Z.S. Mohammed Saleem et al. discontinuation of medications. In addition, it was shown that better T-cell response and increased levels of neutralizing anti- bodies against the virus were developed after preemptive therapy when compared to patients who received prophy- laxis.11-13 Such an immune response that developed after preemptive therapy may prevent relapse and further CMV infections after transplant.11-13 In this study, the CMV profile of all transplant patients was D+/R+. Prophylaxis was not given to the patients with strict follow up by CMV-RTPCR for three months. In this study, CMV-RTPCR tested positive in the first month post-transplant in 22.4% of our patients. The course of the disease was benign and did not impact the graft function. The low rate of infection might be explained by that all our patients were positive for IgG. On the other hand, the benign course of the disease can be explained by the difference in CMV genotype that may cause the disease. It was previously shown that different CMV genotypes may influence the severity and the outcome of CMV infection in organ transplant patients.14,15 CMV genotype study has not been performed in our country, therefore more studies are recom- mended investigating CMV genotypes and their association with disease severity and outcomes. In contrast to other studies,16 no association was found between age and incidence of CMV infection. In agreement with another study,16 gender was not associated with the incidence of CMV infection. In a previous study, it was found that older donor was associated with an increased risk of CMV infection post-transplant. We found a significant relationship between younger donor age and CMV positivity. This is difficult to explain and further studies are required to investigate the impact of donor age upon CMV infection. Our study has limitations. First, this is a two centers observation study with patients all D+/R+. Second, the follow up duration was 6 months and it is unknown what the further outcome was. Our results suggested that further studies are needed recruiting D+/R– patients and the use of such an approach for those patients and longer follow up dura- tion is needed to investigate the impact of preemptive therapy on the long-term outcome and graft survival.  References 1. Naqid IA, Yousif SH, Hussein NR. Serological study of IgG and IgM antibodies to cytomegalovirus and toxoplasma infections in pregnant women in Zakho City, Kurdistan Region, Iraq. 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