- Email: [email protected]
Cytomegalovirus Disease After Kidney Transplantation: Clues to Accurate Diagnosis
Cytomegalovirus Disease After Kidney Transplantation: Clues to Accurate Diagnosis E. Nemati, M. Eizadi, M. Moghani Lankarani, B. Kardavani, H.-R. Khoddami-Vishteh, E. Kalantar, M. Lesan-Pezeshki, H. Khedmat, and A.R. Saadat ABSTRACT Background. The clinical diagnosis of cytomegalovirus (CMV) disease after kidney transplantation is often not accurate. We evaluated the factors associated with a correct diagnosis of CMV disease in these patients. Materials and Methods. This retrospective study of all renal transplant patients between 2004 and 2005 with a clinical diagnosis of CMV disease included both donors and recipients who were seropositive for CMV at transplantation. We assessed the rate and correlated factors with a correct diagnosis. Results. Among 127 cases, the 30 (23.6%) patients who had a correct diagnosis of CMV disease. Showed higher ages at transplantation (48.8 ⫾ 15.3 vs. 39.8 ⫾ 14.4 years; P ⫽ .004) and a shorter interval between transplantation and symptom presentation (9.7 ⫾ 20.7 vs. 25.6 ⫾ 33.6 days; P ⫽ .048). Diabetes mellitus (DM) was the cause of end-stage renal disease (ESRD) in 41% of patients with a correct diagnosis, whereas it was the cause in 11% of CMV disease-negative patients (P ⬍ .001). A multiple logistic regression model showed that DM as the cause of ESRD (P ⫽ .001; odds ratio [OR] 16.331), ⬎5 months duration between transplantation and the presence of symptoms (P ⫽ .001; OR, 0.060), and age at transplantation ⬎55 years (P ⫽ .022; OR, 3.833) were predictors of a correct diagnosis of CMV disease (2 ⫽ 46.45; P ⬍ .001). Conclusion. The results herein showed that considering some variables significantly improved the accuracy of a correct diagnosis of CMV disease after kidney transplantation.
C
YTOMEGALOVIRUS (CMV) disease is a significant cause of morbidity and mortality after organ transplantation.1 Furthermore, there is indirect evidence that CMV disease itself is an independent risk factor for acute and chronic allograft rejection.2 Among the several modalities proposed to prevent CMV disease among kidney recipient patients, one of the most recommended strategies is antiviral prophylaxis.3 However, some authors have raised concerns about possible side effects, about emergence of CMV resistance, and about the expense of this policy.4 An alternative is posttransplant surveillance, which comes in two forms: deferred and preemptive strategies.5 A deferred strategy involves regular assessment of patients and early treatment of the disease; in the preemptive strategy closely monitors subjects for blood levels of antibodies with treatment when tests for CMV infection become positive, before the onset of clinical features of disease. The preemptive strategy is more complicated and expensive. It is also © 2007 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 39, 987–989 (2007)
not effective in patient populations wherein the majority of donors and recipients are CMV seropositive. Thus, the deferred strategy is the policy of choice in many centers. This method depends on early diagnosis, although some studies have reported that clinical manifestations, alone, are not accurate for a proper diagnosis of CMV disease.1,6 In this study, we sought to determine the factors that may From the Nephrology/Urology Research Center (NURC), Baqiyatallah Medical Sciences University (E.N.); the Baqiyatallah Medical Sciences University (M.E., E.K., M.L.-P., H.K., A.R.S.), and the Clinical Research Unit, Baqiyatallah Medical Sciences University (M.M.L., B.K., H.-R., K.-V.), Tehran, Iran. Fully supported and funded by Baqiyatallah Medical Sciences University. Address reprint requests to Eghlim Nemati, Baqiyatallah University of Medical Sciences, Vanak Square, Mollasadra Ave. 19945-587, 88037561 - PO Box 14155-6437 - Postal code: 1435915371, Tehran, Iran. E-mail: [email protected] 0041-1345/07/$–see front matter doi:10.1016/j.transproceed.2007.03.087 987
988
help in the correct diagnosis of CMV disease among kidney transplant patients, where in donors and recipients were both seronegative for CMV at transplantation. METHODS AND MATERIALS In a cross-sectional study, we reviewed all records of hospitalizations related to kidney transplant patients seeking cases with a clinical diagnosis of CMV disease between March 2004 and March 2005. Based on our experience that the majority of the recipients and donors were seropositive for CMV, we excluded all cases in which the donor or the recipient were seronegative for CMV at transplantation (D⫺ or R⫺, respectively). We examined the following variables in the patients’ records: age, gender, age at transplantation, previous history of kidney transplantation, the kidney source, cause of end-stage renal disease (ESRD) history of blood transfusion, presenting signs and symptoms, and duration between the transplantation and the presence of symptoms. The immunosuppressive strategy in our center included prednisone, mycophenolate mofetil, and cyclosporine microemulsion formulation (Neoral). Antibiotic prophylaxis against CMV infection was not performed for seropositive patients in our center. The correct diagnosis of CMV disease was defined as CMV antigenemia (positive CMV pp65 determined by ELISA test) plus any of the following: decreased leukocytes or platelets, increased transaminases, or worsening of renal function. After reporting the relative frequency and mean values (standard deviation [SD]) or median of the measured variables, we used SPSS 13 for statistical analysis. To compare the measured variables between the patients with or without a definite diagnosis of CMV disease, we employed independent sample t-test, Mann–Whitney test, and 2 test, based on the variable type. Finally, we entered all the variables into a multiple logistic regression model to evaluate their correlation with the correct diagnosis of CMV disease. P ⬎ .05 was considered significant.
RESULTS
During the study period 130 of 380 inpatient admissions of kidney recipients were clinically diagnosed with CMV disease. Three cases were excluded because they were either D⫺ or R⫺ at transplantation. Of 127 D⫹/R⫹ cases, 90 (70.8%) were men and 37 (29.2%) were women with the mean age of 43.9 ⫾ 16.1 (range, 10 to 75) years. The mean age at transplantation was 42 ⫾ 15.1 (range, 1 to 75) years. The median time between transplantation and the presentation of sign and symptoms was 3.5 months (Q1, Q3: 1.5, 37.6). The causes of ESRD were as follows: hypertension (n ⫽ 30; 23.5%), diabetes mellitus (DM; n ⫽ 25; 19.6%), polycystic kidney disease (n ⫽ 12; 9.8%), glomerulonephritis (n ⫽ 3; 2%), and other causes (n ⫽ 57; 44.8%). Two patients received kidneys from cadavers and the rest from living donors. Four patients (3.2%) had a previous history of kidney transplantation. Forty patients (31.5%) had a positive history of blood transfusion. Ninety patients (70%) presented with fever, 38 (30%) with nausea, and 34 (27%) with vomiting. According to disease definition, 30 (23.6%) subjects had a correct diagnosis of posttransplant CMV disease.
NEMATI, EIZADI, LANKARANI ET AL
The mean age at transplantation was significantly higher among those with a correct diagnosis of CMV disease (48.8 ⫾ 15.3 vs. 39.8 ⫾ 14.4 years; P ⫽ .004; Student t-test). In addition, 40% of these patients and 12.9% of the others had an age of ⬎55 years at transplantation. The mean time between transplantation and presentation of sign and symptoms was significantly lower among patients with a correct diagnosis of CMV disease (9.7 ⫾ 20.7 vs 25.6 ⫾ 33.6 months, P ⫽ .048, Mann–Whitney test). In these patients, this duration was ⬍5 months in 87.5% of patients; 43.2% of the other patients had symptoms in the same period. DM was the cause of ESRD in 41% of patients with a correct diagnosis of CMV disease, and it was the cause in 11% of patients who were CMV disease negative (P ⬍ .001). The other studied variables were not significantly different between the two groups (P ⬎ .05). After entering the variables into a multiple logistic regression model, we observed that DM as the cause of ESRD (P ⫽ .001; OR, 16.331; 95% confidence interval [CI], 3.369 to 79.164), ⬎5 months duration between transplantation and the presence of symptoms (P ⫽ .001; OR, 0.060; 95% CI, 0.011 to 0.318), and age ⬎55 years at transplantation (P ⫽ .022; OR, 3.833; 95% CI, 1.210 to 12.145) were predictors of a correct diagnosis of CMV disease (2 ⫽ 46.45, 3 degrees of freedom; P ⬍ .001). Considering the cutpoint of 0.5, the model has a sensitivity of 60.9%, specificity of 89.7%, positive predictive value of 70.0%, negative predictive value of 85.2% and, an accuracy of 81.5% for the correct diagnosis of CMV disease. DISCUSSION
We observed that based on clinical findings alone the clinical suspicion of nephrologists for a correct diagnosis of CMV disease in D⫹/R⫹ kidney recipients was appropriately 24% of cases. Our findings were concistent with other studies, which reported a lack of accuracy of clinical findings for a proper diagnosis of CMV disease.1,6 The results presented here in showed that by considering DM as the cause of ESRD, age at transplantation ⬎55 years, and the interval between transplantation and the presence of sign and symptoms of ⬍5 month as risk factors, the ability to correctly diagnose CMV disease in clinically suspected D⫹/R⫹ renal transplant patients nearly reached 61%. This value is higher than 40% accuracy in the more sophisticated, costly preemptive method.7 Our findings also supported the previous findings of an association of age 8 and of DM8 –10 with CMV disease. This observation could be due to the suppressive effect of advanced age and DM on the immune system, which increased the risk of developing CMV disease. In contrast to other studies, we did not msbwz any association between CMV disease and gender9 or a positive history of blood transfusion.11 Several studies have also proposed HLA mismatching and CMV serology in donors and recipients,12 prolonged pretransplant dialysis and treatment with mycophenolate mofetil,13 induction therapy with ALG,14 and patient race15 as risk factors for
POSTTRANSPLANT CMV DISEASE
CMV disease. The median time between transplantation and the presentation of sign and symptoms was 3.5 months in our study which supports the reports of previous authors.10,16,17 In conclusion, we observed that by considering some simple data, such as age at transplantation, the duration between transplantation and presentation and the cause of ESRD, the accuracy of a correct diagnosis of CMV disease improved significantly. Further studies are required to find better laboratory and clinical methods for diagnosis of CMV disease after kidney transplantation. REFERENCES 1. Paya CV, Razonable RR: Cytomegalovirus infection after solid organ transplantation. In: Bowden RA, ed. Transplant infections. Philadelphia: Lippincott Williams & Wilkins; 2003, p 298 2. Tolkoff-Rubin NE, Rubin RH: Recent advances in the diagnosis and management of infection in the organ transplant recipient. Semin Nephrol 20:148, 2000 3. Jassal SV, Roscoe JM, Zaltzman JS, et al: Clinical practice guidelines: prevention of cytomegalovirus disease after renal transplantation. J Am Soc Nephrol 9:1697, 1998 4. Emery VC: Prophylaxis for CMV should not now replace pre-emptive therapy in solid organ transplantation. Rev Med Virol 11:83, 2001 5. Brennan DC, Storch GA, Lippman BJ: Preemptive ganciclovir therapy in renal transplantation. Ann Intern Med 124:693, 1996 6. Cransberg K, Marlies Cornelissen EA, Davin JC, et al: Improved outcome of pediatric kidney transplantations in the Netherlands— effect of the introduction of mycophenolate mofetil? Pediatr Transplant 9:104, 2005 7. Geddes CC, Church CC, Collidge T, et al: Management of cytomegalovirus infection by weekly surveillance after renal trans-
989 plant: analysis of cost, rejection and renal function. Nephrol Dial Transplant 18:1891, 2003 8. Yango A, Morrissey P, Zanabli A, et al: Comparative study of prophylactic oral ganciclovir and valacyclovir in high-risk kidney transplant recipients. Nephrol Dial Transplant 18:809, 2003 9. Pouteil-Noble C, Ecochard R, Landrivon G, et al: Cytomegalovirus infection--an etiological factor for rejection? A prospective study in 242 renal transplant patients. Transplantation 55:851, 1993 10. Keay S: CMV infection and disease in kidney and pancreas transplant recipients. Transpl Infect Dis 1 (Suppl 1):19, 1999 11. Dunn DL, Mayoral JL, Gillingham KJ, et al: Treatment of invasive cytomegalovirus disease in solid organ transplant patients with ganciclovir. Transplantation 51:98, 1991 12. Peterson PK, Balfour HH Jr, Marker SC, et al: Cytomegalovirus disease in renal allograft recipients: a prospective study of the clinical features, risk factors and impact on renal transplantation. Medicine (Baltimore) 59:283, 1980 13. Abbott KC, Hypolite IO, Viola R, et al: Hospitalizations for cytomegalovirus disease after renal transplantation in the United States. Ann Epidemiol 12:402, 2002 14. Hanto DW, Jendrisak MD, So SK, et al: Induction immunosuppression with antilymphocyte globulin or OKT3 in cadaver kidney transplantation. Results of a single institution prospective randomized trial. Transplantation 57:377, 1994 15. Meier-Kriesche HU, Ojo A, Magee JC, et al: AfricanAmerican renal transplant recipients experience decreased risk of death due to infection: possible implications for immunosuppressive strategies. Transplantation 70:375, 2000 16. Kyllonen L, Kahu J, Kyllonen L, et al: Kidney transplantation from 1119 deceased donors in Finland, 1991 to 2003: impact of donor factors. Transplant Proc 37:3248, 2005 17. Pour-Reza-Gholi F, Labibi A, Farrokhi F, et al: Signs and symptoms of cytomegalovirus disease in kidney transplant recipients. Transplant Proc 37:3056, 2005
C
YTOMEGALOVIRUS (CMV) disease is a significant cause of morbidity and mortality after organ transplantation.1 Furthermore, there is indirect evidence that CMV disease itself is an independent risk factor for acute and chronic allograft rejection.2 Among the several modalities proposed to prevent CMV disease among kidney recipient patients, one of the most recommended strategies is antiviral prophylaxis.3 However, some authors have raised concerns about possible side effects, about emergence of CMV resistance, and about the expense of this policy.4 An alternative is posttransplant surveillance, which comes in two forms: deferred and preemptive strategies.5 A deferred strategy involves regular assessment of patients and early treatment of the disease; in the preemptive strategy closely monitors subjects for blood levels of antibodies with treatment when tests for CMV infection become positive, before the onset of clinical features of disease. The preemptive strategy is more complicated and expensive. It is also © 2007 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 39, 987–989 (2007)
not effective in patient populations wherein the majority of donors and recipients are CMV seropositive. Thus, the deferred strategy is the policy of choice in many centers. This method depends on early diagnosis, although some studies have reported that clinical manifestations, alone, are not accurate for a proper diagnosis of CMV disease.1,6 In this study, we sought to determine the factors that may From the Nephrology/Urology Research Center (NURC), Baqiyatallah Medical Sciences University (E.N.); the Baqiyatallah Medical Sciences University (M.E., E.K., M.L.-P., H.K., A.R.S.), and the Clinical Research Unit, Baqiyatallah Medical Sciences University (M.M.L., B.K., H.-R., K.-V.), Tehran, Iran. Fully supported and funded by Baqiyatallah Medical Sciences University. Address reprint requests to Eghlim Nemati, Baqiyatallah University of Medical Sciences, Vanak Square, Mollasadra Ave. 19945-587, 88037561 - PO Box 14155-6437 - Postal code: 1435915371, Tehran, Iran. E-mail: [email protected] 0041-1345/07/$–see front matter doi:10.1016/j.transproceed.2007.03.087 987
988
help in the correct diagnosis of CMV disease among kidney transplant patients, where in donors and recipients were both seronegative for CMV at transplantation. METHODS AND MATERIALS In a cross-sectional study, we reviewed all records of hospitalizations related to kidney transplant patients seeking cases with a clinical diagnosis of CMV disease between March 2004 and March 2005. Based on our experience that the majority of the recipients and donors were seropositive for CMV, we excluded all cases in which the donor or the recipient were seronegative for CMV at transplantation (D⫺ or R⫺, respectively). We examined the following variables in the patients’ records: age, gender, age at transplantation, previous history of kidney transplantation, the kidney source, cause of end-stage renal disease (ESRD) history of blood transfusion, presenting signs and symptoms, and duration between the transplantation and the presence of symptoms. The immunosuppressive strategy in our center included prednisone, mycophenolate mofetil, and cyclosporine microemulsion formulation (Neoral). Antibiotic prophylaxis against CMV infection was not performed for seropositive patients in our center. The correct diagnosis of CMV disease was defined as CMV antigenemia (positive CMV pp65 determined by ELISA test) plus any of the following: decreased leukocytes or platelets, increased transaminases, or worsening of renal function. After reporting the relative frequency and mean values (standard deviation [SD]) or median of the measured variables, we used SPSS 13 for statistical analysis. To compare the measured variables between the patients with or without a definite diagnosis of CMV disease, we employed independent sample t-test, Mann–Whitney test, and 2 test, based on the variable type. Finally, we entered all the variables into a multiple logistic regression model to evaluate their correlation with the correct diagnosis of CMV disease. P ⬎ .05 was considered significant.
RESULTS
During the study period 130 of 380 inpatient admissions of kidney recipients were clinically diagnosed with CMV disease. Three cases were excluded because they were either D⫺ or R⫺ at transplantation. Of 127 D⫹/R⫹ cases, 90 (70.8%) were men and 37 (29.2%) were women with the mean age of 43.9 ⫾ 16.1 (range, 10 to 75) years. The mean age at transplantation was 42 ⫾ 15.1 (range, 1 to 75) years. The median time between transplantation and the presentation of sign and symptoms was 3.5 months (Q1, Q3: 1.5, 37.6). The causes of ESRD were as follows: hypertension (n ⫽ 30; 23.5%), diabetes mellitus (DM; n ⫽ 25; 19.6%), polycystic kidney disease (n ⫽ 12; 9.8%), glomerulonephritis (n ⫽ 3; 2%), and other causes (n ⫽ 57; 44.8%). Two patients received kidneys from cadavers and the rest from living donors. Four patients (3.2%) had a previous history of kidney transplantation. Forty patients (31.5%) had a positive history of blood transfusion. Ninety patients (70%) presented with fever, 38 (30%) with nausea, and 34 (27%) with vomiting. According to disease definition, 30 (23.6%) subjects had a correct diagnosis of posttransplant CMV disease.
NEMATI, EIZADI, LANKARANI ET AL
The mean age at transplantation was significantly higher among those with a correct diagnosis of CMV disease (48.8 ⫾ 15.3 vs. 39.8 ⫾ 14.4 years; P ⫽ .004; Student t-test). In addition, 40% of these patients and 12.9% of the others had an age of ⬎55 years at transplantation. The mean time between transplantation and presentation of sign and symptoms was significantly lower among patients with a correct diagnosis of CMV disease (9.7 ⫾ 20.7 vs 25.6 ⫾ 33.6 months, P ⫽ .048, Mann–Whitney test). In these patients, this duration was ⬍5 months in 87.5% of patients; 43.2% of the other patients had symptoms in the same period. DM was the cause of ESRD in 41% of patients with a correct diagnosis of CMV disease, and it was the cause in 11% of patients who were CMV disease negative (P ⬍ .001). The other studied variables were not significantly different between the two groups (P ⬎ .05). After entering the variables into a multiple logistic regression model, we observed that DM as the cause of ESRD (P ⫽ .001; OR, 16.331; 95% confidence interval [CI], 3.369 to 79.164), ⬎5 months duration between transplantation and the presence of symptoms (P ⫽ .001; OR, 0.060; 95% CI, 0.011 to 0.318), and age ⬎55 years at transplantation (P ⫽ .022; OR, 3.833; 95% CI, 1.210 to 12.145) were predictors of a correct diagnosis of CMV disease (2 ⫽ 46.45, 3 degrees of freedom; P ⬍ .001). Considering the cutpoint of 0.5, the model has a sensitivity of 60.9%, specificity of 89.7%, positive predictive value of 70.0%, negative predictive value of 85.2% and, an accuracy of 81.5% for the correct diagnosis of CMV disease. DISCUSSION
We observed that based on clinical findings alone the clinical suspicion of nephrologists for a correct diagnosis of CMV disease in D⫹/R⫹ kidney recipients was appropriately 24% of cases. Our findings were concistent with other studies, which reported a lack of accuracy of clinical findings for a proper diagnosis of CMV disease.1,6 The results presented here in showed that by considering DM as the cause of ESRD, age at transplantation ⬎55 years, and the interval between transplantation and the presence of sign and symptoms of ⬍5 month as risk factors, the ability to correctly diagnose CMV disease in clinically suspected D⫹/R⫹ renal transplant patients nearly reached 61%. This value is higher than 40% accuracy in the more sophisticated, costly preemptive method.7 Our findings also supported the previous findings of an association of age 8 and of DM8 –10 with CMV disease. This observation could be due to the suppressive effect of advanced age and DM on the immune system, which increased the risk of developing CMV disease. In contrast to other studies, we did not msbwz any association between CMV disease and gender9 or a positive history of blood transfusion.11 Several studies have also proposed HLA mismatching and CMV serology in donors and recipients,12 prolonged pretransplant dialysis and treatment with mycophenolate mofetil,13 induction therapy with ALG,14 and patient race15 as risk factors for
POSTTRANSPLANT CMV DISEASE
CMV disease. The median time between transplantation and the presentation of sign and symptoms was 3.5 months in our study which supports the reports of previous authors.10,16,17 In conclusion, we observed that by considering some simple data, such as age at transplantation, the duration between transplantation and presentation and the cause of ESRD, the accuracy of a correct diagnosis of CMV disease improved significantly. Further studies are required to find better laboratory and clinical methods for diagnosis of CMV disease after kidney transplantation. REFERENCES 1. Paya CV, Razonable RR: Cytomegalovirus infection after solid organ transplantation. In: Bowden RA, ed. Transplant infections. Philadelphia: Lippincott Williams & Wilkins; 2003, p 298 2. Tolkoff-Rubin NE, Rubin RH: Recent advances in the diagnosis and management of infection in the organ transplant recipient. Semin Nephrol 20:148, 2000 3. Jassal SV, Roscoe JM, Zaltzman JS, et al: Clinical practice guidelines: prevention of cytomegalovirus disease after renal transplantation. J Am Soc Nephrol 9:1697, 1998 4. Emery VC: Prophylaxis for CMV should not now replace pre-emptive therapy in solid organ transplantation. Rev Med Virol 11:83, 2001 5. Brennan DC, Storch GA, Lippman BJ: Preemptive ganciclovir therapy in renal transplantation. Ann Intern Med 124:693, 1996 6. Cransberg K, Marlies Cornelissen EA, Davin JC, et al: Improved outcome of pediatric kidney transplantations in the Netherlands— effect of the introduction of mycophenolate mofetil? Pediatr Transplant 9:104, 2005 7. Geddes CC, Church CC, Collidge T, et al: Management of cytomegalovirus infection by weekly surveillance after renal trans-
989 plant: analysis of cost, rejection and renal function. Nephrol Dial Transplant 18:1891, 2003 8. Yango A, Morrissey P, Zanabli A, et al: Comparative study of prophylactic oral ganciclovir and valacyclovir in high-risk kidney transplant recipients. Nephrol Dial Transplant 18:809, 2003 9. Pouteil-Noble C, Ecochard R, Landrivon G, et al: Cytomegalovirus infection--an etiological factor for rejection? A prospective study in 242 renal transplant patients. Transplantation 55:851, 1993 10. Keay S: CMV infection and disease in kidney and pancreas transplant recipients. Transpl Infect Dis 1 (Suppl 1):19, 1999 11. Dunn DL, Mayoral JL, Gillingham KJ, et al: Treatment of invasive cytomegalovirus disease in solid organ transplant patients with ganciclovir. Transplantation 51:98, 1991 12. Peterson PK, Balfour HH Jr, Marker SC, et al: Cytomegalovirus disease in renal allograft recipients: a prospective study of the clinical features, risk factors and impact on renal transplantation. Medicine (Baltimore) 59:283, 1980 13. Abbott KC, Hypolite IO, Viola R, et al: Hospitalizations for cytomegalovirus disease after renal transplantation in the United States. Ann Epidemiol 12:402, 2002 14. Hanto DW, Jendrisak MD, So SK, et al: Induction immunosuppression with antilymphocyte globulin or OKT3 in cadaver kidney transplantation. Results of a single institution prospective randomized trial. Transplantation 57:377, 1994 15. Meier-Kriesche HU, Ojo A, Magee JC, et al: AfricanAmerican renal transplant recipients experience decreased risk of death due to infection: possible implications for immunosuppressive strategies. Transplantation 70:375, 2000 16. Kyllonen L, Kahu J, Kyllonen L, et al: Kidney transplantation from 1119 deceased donors in Finland, 1991 to 2003: impact of donor factors. Transplant Proc 37:3248, 2005 17. Pour-Reza-Gholi F, Labibi A, Farrokhi F, et al: Signs and symptoms of cytomegalovirus disease in kidney transplant recipients. Transplant Proc 37:3056, 2005