Vascular Complication and Doppler Ultrasonographic Finding After Renal Transplantation

Technical aspects

Vascular Complication and Doppler Ultrasonographic Finding After Renal Transplantation M.K. Tarzamni, H. Argani, M. Nurifar, and N. Nezami ABSTRACT Objectives. Vascular complications are common after renal transplantation. In this study we correlated Doppler sonographic indices and transplant kidney function. Methods. We reviewed data on 244 renal transplant patients. Doppler ultrasonographic evaluation was performed during the first 2 weeks after renal transplantation. We determined resistive index (RI) and pulsatility index (PI) in the interlobar arteries and thrombosis of renal and lower limb veins. Serum creatinine (Cr) and cyclosporine levels were evaluated prior to sonographic assessment. Results. The mean age of the 142 male and 102 female patients was 36.31 ⫾ 3.30 years. Prevalence of real artery stenosis was 9.5%. In these patients the mean serum Cr level (2.21 ⫾ 1.83 mg/dL) was significantly higher than among patients with patent renovascular tributary (1.49 ⫾ 1.00 mg/dL; P ⫽ .03). RI and PI were also significantly correlated with serum Cr(P ⫽ .05 and .001, respectively). There was no relationship between cyclosporine level or panel-reactive antibody with RI and PI. Retransplant patients showed higher RI than first renal allograft recipients (0.72 ⫾ 0.16 vs 0.63 ⫾ 0.11; P ⫽ .006). Serum Cr level was higher among renal allograft recipients with Doppler evidence of thrombosis of the lower limb veins (3.1 ⫾ 0.98 mg/dL versus 1.56 ⫾ 1.13 mg/dL; P ⫽ .04). Conclusions. RI and PI are two valuable Doppler ultrasonographic markers to determine renal allograft function and related vascular complications.

R

ENAL TRANSPLANTATION is the treatment of choice for patients with end-stage renal disease.1,2 It continues to be the most commonly performed solid organ transplant with more than 10,000 procedures last year in the United States.3 Following surgical procedures, urologic and vascular complications do occur after transplantation. They may have a substantial impact on morbidity and mortality. Urologic complications occur in 4% to 8% of patients, and vascular complications, approximately 1% to 2%.4

The aim of this study was to determine the incidence of vascular complications of the renal transplant artery and vein and to analyze their correlation with laboratory and ultrasonographic findings. From the Department of Radiology, Imam Hospital, Tabriz University of Medical Science, East Azerbaijan, Iran. Address reprint requests to M. K. Tarzamni, Department of Radiology, Imam Hospital, Tabriz University of Medical Science, Tabriz, East Azerbaijan, Iran. E-mail: [email protected]

0041-1345/07/$–see front matter doi:10.1016/j.transproceed.2007.02.004

© 2007 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710

1098

Transplantation Proceedings, 39, 1098 –1102 (2007)

VASCULAR COMPLICATIONS POSTTRANSPLANTATION

1099

METHODS AND MATERIALS Our retrospective study surveyed 244 transplant recipients transplanted between November 2002 and March 2006. All of the patients underwent Doppler ultrasonography during the first 2 weeks while staying in the transplantation ward. All sonographies were performed using an Hitachi model EUB 525 with convex probes (3.5 and 7.5 MHz) by one sonographist. Doppler ultrasonography indices were evaluated: resistive index (RI), pulsatility index (PI), and percent lumuiol stenosis. Laboratory data such as serum creatinine (by Jaffe method) and cyclosporine trough level (by radioimmunoassay) were determined just prior to an ultrasonographic evaluation. Pretransplant panel-reactive antibody level was considered for each patient. Vascular complications were divided into two groups: early complications, including renal artery and vein thrombosis occurring within the first 2 days posttransplantation, and vascular complications such as transplant renal artery stenosis (TRAS) occurring from the first month to years after transplantation.5–7 Statistical analyses were performed by SPSS 13.0 for windows software package (SPSS, Chicago, Ill, USA). Results are presented as mean values and standard deviations. Statistical significance between compared groups was estimated using independent Sample t tests and nonparametric Mann-Whitney U tests. The results were considered significant when the P value was ⬍.05.

RESULTS

In our analysis studies on 244 transplant patients were reviewed. There were 142 men (58.2%) and 102 women (41.8%). The mean duration of hospital stay was 26.54 ⫾ 11.94 days. Seventeen patients (7%) were retransplants. The mean patient age was 36.31 ⫾ 13.30 years (median, 36 years old). Among 244 patients, 30 individuals (12.3%) experienced vascular complication of their transplanted kidney such as renal artery and vein thrombosis and renal artery stenosis. Among the 30 patients, 4 (1.6%) displayed renal vein thrombosis; 3 (1.2%), renal artery thrombosis; and 23 patients (9.5%), renal artery stenosis. In the last group 19 cases (7.8%) were moderate (50% to 70% of artery lumen) and 4 (1.6%) severe (⬎70% artery lumen).

Fig 1. Resistive index (Mean ⫾ SD) difference between two groups of patients with and without TRAS.

Fig 2. Pulsatility index (mean ⫾ SD) difference between two groups of patients with and without TRAS.

All patients with renal artery and vein thrombosis experienced graft loss. Two patients had sonographic evidence of lower limb vein thromboses, including one who also had renal vein thrombosis. The mean serum creatinine level in all patients was 1.57 ⫾ 1.13 mg/dL. It was 2.21 ⫾ 1.83 mg/dL among patients with TRAS, which was higher than that in patients with patent renovascular tributary (1.49 ⫾ 1.00 mg/dL; P ⫽ .032). The mean cyclosporine level of all kidney transplant patients was 285.62 ⫾ 139.99 ng/dL, There was no significant difference between TRAS patients and nonTRAS patients (259.57 ⫾ 157.29 ng/dL vs 288.31 ⫾ 138.22 ng/dL; P ⬎ .05). The mean panel-reactive antibody content in patients was 2.71% ⫾ 7.13%; its level in TRAS patients was 9.43% ⫾ 1.96% compared with non-TRAS patients who had a mean panel-reactive antibody level of 6.84% ⫾ 0.46% (P ⬎ .05). Therefore, there was no relation between transplant renal artery stenosis and preoperative panelantibody level. The mean RI and PI of patients were 0.63 ⫾ 0.12 and 1.12 ⫾ 0.37, respectively. Comparison of the two groups of patients (with and without TRAS) showed significantly different RI and PI values. Both RI and PI values were lower among the patients with TRAS (P ⫽ .043 and P ⫽ .032, respectively; Figs 1 and 2). Also there was no correlation between patient age versus RI and PI values. The amounts of all the variables with regard to the presence versus absence of renal artery stenosis are presented in Tables 1 and 2. Pearson correlation analysis showed a strong significant linear correlation between RI and PI (P ⫽ .000, coefficient ⫽ ⫹0.712). Interestingly, RI and PI also displayed significant direct linear correlations with serum creatinine level (respectively, P ⫽ .05; coefficient ⫽ ⫺0.126 and P ⫽ .001; coefficient ⫽ ⫺0.209). Figures 3 and 4 show the plots of linear regression analysis between creatinine and RI and PI, respectively. There were no relations between cyclosporine level or panel-reactive antibody with RI and PI. Retransplant patients displayed higher RI than first renal allograft

1100

TARZAMNI, ARGANI, NURIFAR ET AL Table 1. Mean Value of Variables in Two Patient Groups With and Without TRAS Value (Mean ⫾ SD)

Age of patients Resistive index Pulsatility index Panel-reactive antibody Period of admission Patients serum creatinine Cyclosporine level

TRAS

Non-TRAS

Total

P Value

39.30 ⫾ 13.99 0.57 ⫾ 0.16 .96 ⫾ .41 4.66 ⫾ 9.43 24.09 ⫾ 8.39 2.21 ⫾ 1.83 259.57 ⫾ 157.29

36.00 ⫾ 13.22 0.64 ⫾ 0.11 1.14 ⫾ .37 2.50 ⫾ 6.84 26.80 ⫾ 12.24 1.49 ⫾ 1.00 288.31 ⫾ 138.22

36.31 ⫾ 13.30 .63 ⫾ .12 1.12 ⫾ .37 2.71 ⫾ 7.13 26.54 ⫾ 11.94 1.57 ⫾ 1.13 285.62 ⫾ 139.99

NS .043 .032 NS NS .032 NS

recipients (0.72 ⫾ 0.16 vs 0.63 ⫾ 0.11; P ⫽ .006). Serum creatinine levels were higher among renal allograft recipients with Doppler evidence of thrombosis of lower limb veins (3.1 ⫾ 0.98 mg/dL versus 1.56 ⫾ 1.13 mg/dL; P ⫽ .04). DISCUSSION

Doppler ultrasonography not only is a useful tool for early evaluation of transplant kidney vascular status and possible graft insufficiency,8 –10 but also a reliable, noninvasive, easily available tool to identify subjects who may benefit from kidney graft revascularization as well as to assess the effectiveness, of the procedure.11 In this study, the same results and usefulness was observed in the early diagnosis of transplant kidney vascular thrombosis and renal artery stenosis. So patients with renal artery and vein thrombosis and renal artery stenosis were diagnosed noninvasively as rapidly as possible. Although TRAS is relatively rare, its diagnosis is extremely important because early intervention makes possible graft conservation. Therefore, Doppler sonography is an excellent method to screen patients suspected to have TRAS, allowing selection of those subjects who should undergo digital subtraction arteriography.12 According to previous reports, renal artery stenosis is found in 1% to 23% of all renal allograft recipients.13–19 In Iran in 2005, the number was 10%.20 In our study the prevalence of transplant renal artery stenosis was 9.5%. Our prevalence was similar to other reports, but in the study of Sözen et al, its prevalence was 2.3% in children,21 which is lower than our study possibly because of the better wound healing in children. Renal artery thrombosis is an uncommon event with an incidence of less than 1%.22–24 In our study it presented in

more cases, which may be due to technical problems, such as intimal dissection or vessel kinking or torsion related to risk factors of hypotension, multiple renal arteries, unidentified intimal flap, and hypercoagulable state.22,25–26 In addition to renal artery thrombosis, the prevalence of renal vein thrombosis was similar to that reported in other studies, ranging between 0.3% and 4.2%.27–29 Its prevalence in our study was 1.2%. Its causes were same as those of arterial thrombosis, in addition to compression by hematomas or lymphoceles, anastomotic stenosis, and extension of an underlying deep venous thrombosis.22 Chudek et al observed a significant negative correlation between donor glomerular filtration rate (GFR) and PI or RI.30 We considered serum creatinine level as an indier of renal function and GFR and observed a direct linear correlation with RI and PI. Other factors may affect RI and PI namely, arterial blood pressure, heart rate, and vascular compliance. Also the vascular compliance of the graft itself, transplant function, and drugs, induce vasoconstriction for example cyclosporine may alter intrarenal Doppler indices.31–34 In another study, Ardalan et al showed a significant correlation between RI or PI indices with serum creatinine level during first month after renal transplantation.35 Our study also suggested a linear, positive relationship between serum Cr and PI/RI. Normally, the diastolic velocity approaches 50% of peak systolic velocity. With increased resistance, this value decreased and the RI increased. Renal artery stenosis reduces renal perfusion, causing elevation of the serum creatinine level. But because of the decreased peak systolic velocity, the RI is less than 0.5 (Trades pavus pattern).36,37 In 2 Iran studies—2005 and 2006 —the mean RI values for transplanted patients were 0.61 ⫾ 0.08 and 0.57 ⫾ 0.55,20,38 which were lower than

Table 2. Mean Value of Variables in Two Patient Gender Groups Value (Mean ⫾ SD)

Age of patients Resistive index Pulsatility index Panel-reactive antibody Period of admission Patients serum creatinine Cyclosporine level

Male

Female

Total

P Value

35.01 ⫾ 13.69 0.63 ⫾ 0.12 1.10 ⫾ 0.38 2.89 ⫾ 7.55 26.37 ⫾ 12.69 1.65 ⫾ 1.19 270.86 ⫾ 135.96

38.12 ⫾ 12.58 0.64 ⫾ 0.12 1.15 ⫾ 0.36 2.46 ⫾ 6.54 26.76 ⫾ 10.89 1.45 ⫾ 1.04 306.40 ⫾ 143.64

36.31 ⫾ 13.30 .63 ⫾ .12 1.12 ⫾ .37 2.71 ⫾ 7.13 26.54 ⫾ 11.94 1.57 ⫾ 1.13 285.62 ⫾ 139.99

NS NS NS NS NS NS NS

VASCULAR COMPLICATIONS POSTTRANSPLANTATION

those in our assessment. Statistical analysis of the Drudi study showed a significant difference between RI values measured on normal and pathological grafts.11,39 Our study also observed a significant difference among TRAS versus unaffected patients. When we used the cut point of 0.5 for the RI value, there was a significant relation to TRAS. Ardalan et al also reported a correlation between RI and PI,35 the same result was observed herein. Although these two sonographic indices reflect renal interlobular resistance and the decreased RI and increased PI represent renal artery stenosis, these two factors show a linear correlation. RI and PI obtained from intrarenal arteries of the native kidney rise with age in normotensive and hypertensive subjects.40,41 However, we did not found any relation between these two factors. Some reports suggested that posttransplant renal function within a few days after transplantation or at the time of hospital discharge correlated with long-term survival.42 In the Kahraman study, there was a negative correlation between either RI or PI and the 1-month or 1-year creatinine clearance values, respectively. Also, there was no correlation between serum creatinine and both RI-PI values. The current and two other studies demonstrated that Doppler ultrasonography (RI and PI indices) performed in first week after transplantation may be a valuable method to predict allograft function in stable cases in the first week.9,32,42 In another study in Germany, a significant correlation was reported between RI, PI, and creatinine clearance upon univariate analysis.42 The studies of Khosroshahi et al and Ardalan et al also showed the correlation between RI and PI with serum creatinine level.20,35 Our results showed a significant correlation between RI, PI, and serum creatinine level as kidney function indices. The same result was previously presented by Ardalan et al and Krumme,42 in part the same and in part different, from the Kahraman et al findings.9 Supporting our finding, Radermacher et al in Germany recently reported that RI was the strongest predictor of a decline in creatinine

1101

Fig 4.

Linear regression between PI and creatinine.

clearance, the need for dialysis, and death in addition to other parameters.43 Gaschen et al showed that application of ultrasonographic imaging provided valuable data about the functional state of a renal graft in a nonhuman primate renal transplant model. Ultrasonography showed scores a better predictive value of histology than serum creatinine values alone.44 In another study in Slovenia,45 there was no significant difference in serum creatinine between stenosis and control group, that conclusions that are similar to those that we have presented. Theoretically cyclosporine may increase the intrarenal vascular resistance,35 but there was no correlation between RI and cyclosporine level.35 The results of our findings, like in this study, did not show any correlation as well as; the level of cyclosporine did not differ between the patient groups with versus without TRAS. In counterpart to previous studies,46,47 it seems that we should not consider cyclosporine as the culprit in TRAS pathophysiology. In conclusion, the prevalence of vascular complications was similar to previous reports from various centers, namely about 10% (12.3%) of all transplant patients. TRAS was a common vascular complication. There was a strong correlation with PI. Because of the significant correlation between the Doppler sonographic indices of RI and PI with serum creatinine level as a kidney function indexs, we can use Doppler sonography as tool to predict renal function in association with the serum creatinine level. But there was no relation between RI and PI versus cyclosporine level.

REFERENCES

Fig 3. Linear regression between RI and creatinine.

1. Suthanthiran M, Strom TB: Renal transplantation. N Engl J Med 331:365, 1994 2. Akbar SA, Zafar S, Jafri H, et al: Complications of Renal Transplantation. Radiographics 25:1335, 2005 3. Terasaki PI, Cecka JM, Gjertson DW, et al: High survival rates of kidney transplants from spousal and living unrelated donors. N Engl J Med 333:333, 1995

1102 4. Kocak T, Nane I, Ander H, et al: Urological and surgical complications in 362 consecutive living related donor kidney transplantations. Urol Int 72:252, 2004 5. Danovitch GM: Handbook of Kidney transplantation. Boston: Little, Brown, and Company; 1992 6. Jirasiritham S, Tapaneeyakam J, Tirapanitch W, et al: Transplant renal artery stenosis in Thailand. J Med Assoc Thai 87:304, 2004 7. Humar A, Matas AJ: Surgical complications after kidney transplantation. Semin Dial 18:505, 2005 8. Cofan F, Gilabert R, Oppenheimer F, et al: Duplex-Doppler ultrasound and MAG-3 scintigraphy in the evaluation of acute tubular necrosis after kidney transplantation. Transplant Proc 39:1376, 1997 9. Kahraman S, Genctoy G, Cil B, et al: Prediction of renal allograft function with early Doppler ultrasonography. Transplant Proc 36:1348, 2004 10. Alvarez G, Gonzalez-Molina M, Cabello M, et al: Pulsed and continuous Doppler evaluation of renal dysfunction after kidney transplantation. Eur J Radiol 12:108, 1991 11. Bruno S, Ferrari S, Remuzzi G, et al: Doppler ultrasonography in posttransplant renal artery stenosis: a reliable tool for assessing effectiveness of revascularization? Transplantation 76: 147, 2003 12. de Morais RH, Muglia VF, Mamere AE, et al: Duplex Doppler sonography of transplant renal artery stenosis. J Clin Ultrasound 31:135, 2003 13. Karakayah H, Basaran O, Moray G, et al: Major postoperative complications of renal transplantation: results from a single center in Turkey. Transplant Proce 35:2657, 2003 14. Fervenza FC, Lafayette RA, Alfrey EJ, et al: Renal artery stenosis in kidney transplants. Am J Kidney Dis 31:142, 1998 15. Vaiculescu A, Hollenbeck M, Plum J, et al: Iliac artery stenosis proximal to a kidney transplant. Clinical findings, duplexsonographic criteria, treatment, and outcome. Transplantation 76:332, 2003 16. Roberts JP, Ascher NL, Fryd DS, et al: Transplant renal artery stenosis. Transplantation 48:580, 1989 17. Smith RB, Cosimi AB, Lordon R, et al: Diagnosis and management of arterial stenosis causing hypertension after successful renal transplantation. J Urol 115:639, 1976 18. Sankari BR, Geisinger M, Zelch M, et al: Post-transplant renal artery stenosis: impact of therapy on long-term kidney function and blood pressure control. J Urol 155:1860, 1996 19. Fervenza FC, Lafayette RA, Alfrey EJ, et al: Renal artery stenosis in kidney transplants. Am J Kidney Dis 31:142, 1998 20. Khosroshahi HT, Tarzamni M, Oskuii RA: Doppler ultrasonography before and 6 to 12 months after kidney transplantation. Transplant Proc 37:2976, 2005 21. Sözen H, Dalgic A, Karakayali H, et al: Renal transplantation in children. Transplant Proc 38:426, 2006 22. Guirguis N, Buisavljevic MN, Self S, et al: Acute renal artery and vein thrombosis after renal transplant, associated with a short partial thromboplastin time and factor V Leiden mutation. Ann Clin Lab Sci 30:75, 2000 23. Louridas G, Botha JR, Meyers AM, et al: Vascular complications of renal transplantation. The Johannesburg experience. Clin Transpl 1:240, 1987 24. Vidne BA, Leapman SB, Butt KM, et al: Vascular complications in human transplantation. Surgery 79:77, 1976 25. Osman Y, Shokeir A, Ali-el-Dein B, et al: Vascular complications after liver donor renal ransplantation. Study of risk factors and effects on graft and patient survival. J Urol 169:859, 2003 26. Humar A, Johnson EM, Gillingham KJ, et al: Venous thromboembolic complications after kidney and kidney-pancreas

TARZAMNI, ARGANI, NURIFAR ET AL transplantation: a multivariate analysis. Transplantation 65:229, 1998 27. Debleke D, Sacks GA, Sandler M: Diagnosis of allograft renal vein thrombosis. Clin Nucl Med 14:415, 1989 28. Duckett T, Bretan P Jr, Cochran ST, et al: Noninvasive radiological diagnosis of renal vein thrombosis in renal transplantation. J Urol 146:403, 1991 29. Merion RM, Calne RY: Allograft renal vein thrombosis. Transplant Proc 17:1746, 1985 30. Chudek J, Kolonko A, Kró R, et al: The intrarenal vascular resistance parameters measured by duplex Doppler ultrasound shortly after kidney transplantation in patients with immediate, slow, and delayed graft function. Transplant Proc 38:42, 2006 31. Breitenseher M, Helbich T, Kainberger F, et al: Farbdopplersonographie von nierentransplantatn: Ermoglicht der Resistive index die Diadnose eiter chronischen Funktionsstorung? Ultraschall Med 15:24, 1994 32. Dia Palo FQ, Rivolta R, Elli A, et al: Effect of cyclosporine A on renal cortical resistances measured by color Doppler flowmetry on renal grafts. Nephron 65:240, 1993 33. Merkus JW, van Asten WN, Hoitsma AJ, et al: Assessment of hemodynamic changes in human kidney grafts induced by cyclosporine infusion. Transplant Int 4:136, 1991 34. Buckley AR, Cooperberg PI, Reeve CE, et al: The distinction between acute renal transplant rejection and cyclosporine nephrotoxicity: value of duplex sonography. AJR AM J Roentgenol 149:521, 1987 35. Ardalan MR, Tarzamni MK, Mortaazavi M, et al: Relation between resistive index and serum creatinine level in first month after renal transplantation. Transplant Proc 35:2628, 2003 36. Saarinen O: Diagnostic value of resistive index of renal transplants in the early postoperative period. Acta Radiol 32:166, 1991 37. Ardalan MR, Tarzamni MK: Renal allograft hemodynamic and diameter changes after living donor transplantation. Transplant Proc 38:388, 2006 38. Drudi FM, Pretagostini R, Padula S, et al: Color Doppler ultrasound in renal transplant: role of resistive index versus renal cortical ratio in the evaluation of renal transplant diseases. Nephron Clin Pract 98:c67, 2004 39. Mostebeck GH, Gossiger HD, Mallek R, et al: effect of heart rate on Doppler measurements of resisitive index in renal arteries. Radiology 175:511, 1990 40. Krumme B, Kirschner T, Gondolf K, et al: Age-dependency of intrarenal resistance index (RI) in patients with essential hypertension. Kidney Int 47:986, 1995 41. Kahraman S, Genctoy G, Cil B, et al: Prediction of renal allograft function with early Doppler ultrasonography. Transplant Proc 36:1348, 2004 42. Krumme B, Grotz W, Kirste G, et al: Determinants of intrarenal Doppler indices in stable renal allografts. J Am Soc Nephrol 8:813, 1997 43. Radermacher J, Mengel M, Ellis S, et al: N Engl J Med 349:115, 2003 44. Gaschen L, Schuurman HJ: Ultrasound score is more predictive than serum creatinine in assessment of cellular rejection in cynomolgus monkey renal allografts. Invest Radiol 37:376, 2002 45. Zupunski A, Buturovic-Ponikvar J: Duplex-Doppler longterm follow-up of renal transplant artery stenosis: case controlled study. Ther Apher Dial 9:265, 2005 46. Sawaya B, Provenzano R, Kupin WL, et al: Cyclosporin induced renal macroangiopathy. Am J Kidney Dis 12:534, 1988 47. Mathieson P, Jolliffe D, Dudley C, et al: The spouse as a kidney donor: ethically sound? Nephrol Dial Transplant 14:46, 1999