Objectives: A Tc-99m mercaptoacetyltriglycine renal scan has been used to evaluate perfusion and excretory function of renal allografts. A Tc-99m mercaptoacetyltriglycine renal scan has been reported to correlate with early allograft outcomes. This study was done to determine whether a Tc-99m mercaptoacetyltriglycine renal scan has any relation with long-term renal transplant outcomes.

Materials and Methods: A total of 311 consecutive kidney transplant recipients were included in the study. All had Tc-99m mercaptoacetyltriglycine renal scans on posttransplant days 3 and 7. Patterns of the renography curve was graded as follows: 0=normal perfusion and excretion; 1=normal perfusion, reduced excretion; 2=normal perfusion, flat excretion; and 3=reduced perfusion and rising curve. Early postoperative Tc-99m mercaptoacetyltriglycine scintigraphy findings were correlated with serum creatinine values, acute rejection episodes, and
long-term graft survival.

Results: A Tc-99m mercaptoacetyltriglycine renography of a deceased-donor kidney transplant showed a significantly higher grade on both days 3 and 7 than did live-donor kidney transplant (P < .001). Serum creatinine was positively correlated with the renography grades on days 3 and 7. The acute rejection rate was higher in the renography on days 3 and 7. Grade 2 renography on day 3 showed a significantly higher graft failure rate compared with the other grades (8.8% vs 8.6% vs 31.6% vs 7.3%; P = .014). Also, the renography showed the worst 5-year graft survival rate (95.9% vs 93.3% vs 89.5% vs 94.1%; P = .019). There were no differences in the graft failure rate or in graft survival rate according to the Tc-99m mercaptoacetyltriglycine renography grades on day 7.

Conclusions: Our data show that a Tc-99m mercaptoacetyltriglycine renography grade correlate not only with early postoperative kidney function and incidence of acute rejection, but also with long-term outcomes of a renal allograft. A grade 2 renography pattern, with normal uptake and flat excretion, indicates a dismal prognosis for the long-term allograft survival.

Key words : Kidney, Transplant, Prognosis, Renography, Tc-99m-MAG3

Introduction

Renal graft survival has been improving significantly during the last 20 years, since the introduction of new generations of immunosuppressive agents. However, the significant progress that has occurred in renal transplant is driven mostly by improvements in short-term graft survival, but long-term attriti1on is slowing.¹ Short-term endpoints (ie, acute rejection rates) have reduced the use in predicting long-term outcomes as a result of reduced acute rejection rate.^2,3 There are many prospective surrogate markers, which include biochemical, histologic, immunologic, and other measures.³ Several reports of Tc-99m mercaptoacetyltriglycine (MAG3) renography exist as a possible prognostic indicator after a renal transplant, but the late there is limited information regarding the long-term prognostic use of this test.^4-7 Hence, we performed this study to evaluate MAG 3 renography as a surrogate marker in predicting long-term allograft prognosis, using a simplifying renography grade system.

Materials and Methods

We retrospectively analyzed the data from 311 patients who received a renal transplant at the Keimyung University Dongsan Hospital from January 2000, to May 2010. The routine clinical protocol followed by our transplant service includes a standard triple immunosuppressive regimen with tacrolimus, mycophenolate mofetil, and prednisone. Clinical data included serum creatinine, acute rejection, and graft survival, which were collected and analyzed. We defined delayed graft function as a need for dialysis of at least 1 session during the first 7 days after a transplant. Acute rejection included clinical and/or biopsy-proven rejection. Graft failure was defined as a return to maintenance dialysis.

All patients underwent a MAG3 renal scintigraphy on postoperative days 3 and 7. Imaging was obtained on e.cam dual signature gamma camera (Siemens Medical Solutions, West Chicago, IL, USA) and a computer system. A renal scan was performed using an intravenous injection of 500 MBq technetium pertechnetate. After intravenous injection of technetium pertechnetate, a perfusion phase scan obtained 30 frames with 4-second intervals and excretion phase scan obtained 24 frames with 2-minute intervals. The results of the MAG3 renography grade are summarized in Figure 1.

Categoric analyses were performed using the chi-square test. The nonparametric difference between the renography grade groups was tested by the Kruskal-Wallis test. A Kaplan-Meier survival analysis was used to compare graft survivals.

Approval from the institutional review boarder at our hospital was obtained for conducting a retrospective review of the patients’ medical records (IRB number 12-82). All protocols were approved by the ethics committee of the institution before the study began, and the protocols conformed with the ethical guidelines of the 1975 Helsinki Declaration.

Results

Of 311 patients, immediate graft failure was zero. The median recipient age was 40.6 years, and 58% were men. Median follow-up duration was 67 months (Table 1). On posttransplant day 3, one hundred ninety-three renographies were assorted with grade 0, fifty-eight renographies were grade 1, nineteen renographies were grade 2, and forty-one renographies were grade 3. On posttransplant day 7, renography grade distribution was similar to day 3 but, the number of grade 3 significantly decreased from 41 to 20 (Figure 2).

Day 3 renography
The higher renogram grade had an upward tendency with donor age, and donor age in grade 3 was the highest (P = .009). Grade 0 consisted mostly of living donors. A MAG3 scan of a deceased-donor kidney transplant showed a significantly higher grade on day 3 than another living-donor kidney transplant (P < .001). A higher renography grade showed higher serum creatinine levels of day 7 and 1 month after the kidney transplant. The acute rejection rate also was higher in the higher renography grade; whereas grade 0 and 1 had about 10% acute rejection episode, grade 2 had 26%, and grade 3 had 29% (Table 2).

Day 7 renography
A MAG3 renography of a living-donor kidney transplant shows significantly lower grade on day 7 than does a deceased-donor kidney transplant (P = .001). Serum creatinine positively correlated with the day 7 renography grade. Acute rejection rate was higher in the higher renography grade (Table 3).

Renography grade and graft survival
A grade 2 MAG3 renography on day 3 showed a significantly higher graft failure rate compared with the other grades (P = .014) and showed the worst long-term graft survival (P = .019). There was no difference in day 7 renography regarding graft survival and failure rate (Figure 3).

Discussion

Renal scintigraphy has provided clinically important functional evaluation of renal transplants since the beginning of the transplant era. Tc-99m mercaptoacetyltriglycine renal scan has been used as a tool for evaluating perfusion and excretory function of renal allografts.^8-10 Higher renography grade means poorer perfusion and excretion of MAG3. Our data also showed a consistent statistically significant relation between MAG 3 renography grade and posttransplant allograft function in terms of delayed graft function, serum creatinine, and incidence of acute rejection. Renography grade was higher with deceased-donor kidney transplant and high donor age.

Long-term graft survival is an ideal endpoint, but it is limited by longer follow-up requirements and the large cohort of patients required for such studies. Hence, it is important to evaluate alternative short-term surrogate endpoint markers, which can predict long-term renal transplant survival. Several studies have shown that a poor early renography grade predicted early, but not late, graft loss, while some reported that high renography grade was found secondary to long cold and warm ischemia, and predicted late onset of graft function. In our study, we found grade 2 renography on day 3 having worst long-term prognosis. The initial renography in this study was performed on posttransplant day 3. It was found to contain important prognostic information. Grade 2 had a worse long-term prognosis than did grade 3. Grade 2 renography indicates decreased renal function despite preserved perfusion. These results indicate probable loss of functional nephrons in the former group, whereas they indicate preserved vitality in temporarily dysfunctional nephrons in the latter group. Grade 3 renography represents decreased perfusion possibly related to vasospasm. In the study, half of group 3 renography on day 3 was downgraded on day 7, indicating restoration of perfusion with optimal fluid therapy and time.

In conclusion, early postoperative MAG3 renography grade correlates not only with early postoperative kidney function and incidence of acute rejection, but also with long-term outcomes of renal allograft. A MAG3 renography on posttransplant day 3 has useful prognostic information. A grade 2 renography pattern, normal uptake, and flat excretion, indicate a dismal prognosis for long-term allograft survival.

References:

1. Lamb KE, Lodhi S, Meier-Kriesche HU. Long-term renal allograft survival in the United States: a critical reappraisal. Am J Transplant. 2011;11(3):450-462.
   CrossRef - PubMed
2. Marqués GG, Goenaga PE, Royo FJ, Escolá JM, García Fernández N, Unanua AP. Evolution of the renal function is a beter predictor of long-term survival than serum creatinine. Transplant Proc. 2005;37(9):3701-3704.
   CrossRef - PubMed
3. Hariharan S, Kasiske B, Matas A, Cohen A, Harmon W, Rabb H. Surrogate markers for long-term renal allograft survival. Am J Transplant. 2004;4(7):1179-1183.
   CrossRef - PubMed
4. Guignard R, Mourad G, Mariano-Goulart D. Utility of post surgical renal scintigraphy to predict one-year outcome of renal transplants in patients with delayed graft function. Nucl Med Commun. 2011;32(4):314-319.
   CrossRef - PubMed
5. Stevens H, de Klerk JM, Mertens IJ, van Rijk PP, Hené RJ. Quantitative baseline renography 48 hours after renal transplantation predicts long-term graft survival. Eur J Nucl Med. 2001;28(11):1677-1681.
   CrossRef - PubMed
6. Obeidat MA, Luyckx VA, Grebe SO, et al. Post-transplant nuclear renal scans correlate with renal injury biomarkers and early allograft outcomes. Nephrol Dial Transplant. 2011;26(9):3038-3045.
   CrossRef - PubMed
7. Ngai S, Demetriades T. Prediction of long-term renal transplant allograft function from day 3 post-transplant Tc-99m MAG3 scintigraphy. Clin Nucl Med. 2008;33(2):102-105.
   CrossRef - PubMed
8. Bajén MT, Puchal R, González A, et al. MAG3 renogram deconvolution in kidney transplantation: utility of the measurement of initial tracer uptake. J Nucl Med. 1997;38(8):1295-1299.
   PubMed
9. Dubovsky EV, Russell CD, Bischof-Delaloye A, et al. Report of the Radionuclides in Nephrourology Committee for evaluation of transplanted kidney (review of techniques). Semin Nucl Med. 1999;29(2):175-188.
   CrossRef - PubMed
10. Dubovsky EV, Russell CD, Erbas B. Radionuclide evaluation of renal transplants. Semin Nucl Med. 1995;25(1):49-59.
    CrossRef - PubMed