Long-term results of selective renal shielding in patients undergoing total body irradiation in preparation for bone marrow transplantation

Abstract

Summary:own is late or long-term renal toxicity. [2][3][4][5][6][7][8][9][10][11] The renal toxicity described consists of a group of clinical signs including hypertension, anemia, and decreased glomerular filThe purpose of this study was to evaluate the effect of partial renal shielding used in conjunction with total tration rate (GFR) with occasional proteinuria and microscopic hematuria, and edema. Biopsies of the affected body irradiation (TBI) on the incidence of bone marrow transplantation nephropathy (BMT Np) seen as a late kidneys have a unifying aspect in that there is extreme subendothelial widening of the basement membranes, with sequelae after transplantation. Of 402 patients who have undergone bone marrow transplantation (BMT) at the endothelial cell dropout, glomerular arteriolar intimal thickening and atrophic tubules. Whether all the changes seen Medical College of Wisconsin (MCW) 157 were greater than 18 years of age, received 14 Gy TBI and survived on biopsy relate to the 'BMT nephropathy' (BMT Np) previously described has yet to be determined. What is unquesat least 100 days post-transplant. The incidence of BMT nephropathy was evaluated in these patients by dose to tionably true of the data to date is that the use of TBI appears to play a significant role in the development of the the kidneys. In the 72 patients who received 14 Gy TBI with no renal shielding, the actuarial risk of developing syndrome. 5,7-11 Previously, our institution described the use of selective BMT Np at 2. years (30 months) post-BMT was 29 ± 7%. Sixty-eight patients received 14 Gy TBI with partial renal shielding in an effort to reduce the incidence of this late renal toxicity. 7 Here, we found an incidence of partial renal shielding of 15% (renal dose = 11.9 Gy), the actuarial risk of developing BMT Np was 14 ± 5%BMT nephropathy of 26% in the unshielded patients at 18 months vs 6% in the shielded patients (P Ͻ 0.05). Shielding at 2. years. Seventeen patients received 14 Gy TBI with renal shielding of 30% (renal dose = 9.8 Gy); none of utilized at that time was a 70% transmission posterior/ anterior (PA)-only shield that decreased the total renal dose this group have developed BMT Np despite a median follow-up of over 2. years (985 days). The trend of from 14 Gy to 11.9 Gy. Since the partial shielding appeared effective but we were still experiencing some level of late decreasing BMT Np with increasing shielding is statistically significant (P = 0.012). Prognostic factors such as renal toxicity we doubled the shielding to a 40% transmission PA-only block to decrease the dose to the kidneys age, type of transplant and good-risk vs poor-risk disease status were evaluated and were similar in each to 9.8 Gy. Results of this change as well as long-term follow-up of the initial cohort of patients both renally blocked cohort of patients described above. We conclude that given the statistically significant benefit seen here in the and unblocked are the focus of this manuscript. reduced incidence of BMT Np by the use of selectiv...

Loss of renal function following bone marrow transplantation: an analysis of angiotensin converting enzyme D/I polymorphism and other clinical risk factors

“…Our study has also confirmed the previous observation described by Lawton et al 12 that shielding the kidneys during TBI reduces renal injury. At the end of the 3-year follow-up period, the shielded patients had a CrCl that was 62% higher than those who did not.…”

“…Beginning in 1992, the renal shielding was increased to 30% for a resulting renal dose of 9.8 Gy. 12 All patients received GVHD prophylaxis consisting of T cell depletion of the donor marrow and cyclosporine as described previously. 13 There is approximately a 1.7 Ϯ 0.4 log 10 depletion of functional T lymphocytes from the donor marrow.…”

Captopril to Mitigate Chronic Renal Failure After Hematopoietic Stem Cell Transplantation: A Randomized Controlled Trial

“…Chemo-irradiation conditioning was done as described in Lawton et al (8). The standard TBI dose was 14 Gy, in nine equal fractions over three days, using a dose rate of 8 to 20 cGy/minute and with at least four hours between fractions.…”

“…BMT nephropathy in its most severe form appears similar to hemolytic uremic syndrome (HUS), which has also been linked to TBI used for the conditioning regimen (7). Finally, partial kidney shielding at the time of TBI has reduced the occurrence rates of BMT nephropathy (8).…”

Renal pathology in hematopoietic cell transplantation recipients

“…[4][5][6][7] Although exposure of kidneys to radiation during hematopoietic cell transplantation has been hypothesized as a risk factor for bone marrow transplant nephropathy, studies have shown conflicting data regarding renal shielding and long-term renal insufficiency. 5,[8][9][10][11][12] Other causes of thrombotic microangiopathy must be considered in hematopoietic cell transplant recipients, including exacerbation of endothelial injury by chemotherapy, immune-mediated injury, and perhaps most notably, cyclosporine inhibitor toxicity, given as prophylaxis or treatment for graft-versus-host disease.…”