Partial Transmission Kidney Blocks to Reduce Radiation Nephropathy in Patients Receiving Myeloablative Total Body Irradiation

Abstract

Total body irradiation (TBI) is an important component of myeloablative conditioning regimens for patients (pts) with hematologic malignancies requiring allogeneic hematopoietic cell transplant (HCT). It is estimated that 15% of pts undergoing HCT will develop chronic kidney disease (CKD), which can impact long term outcomes and survival. Traditional whole kidney constraints of <15-18 Gy predicts for a <5% risk of dysfunction, but this threshold may be lower for patients undergoing HCT due to multiple risk factors for kidney damage. Acute radiation nephropathy (ARN) is typically defined as new renal dysfunction beginning 6-12 months post-radiation, not associated with acute kidney injury (AKI). We report our institutional experience of partial transmission kidney blocks during myeloablative TBI to decrease the incidence of ARN. From 2015-2018, 45 pts were treated with TBI utilizing partial transmission kidney blocks. Pts were treated standing with 6-10 MV AP/PA beams at extended SSD with a beam spoiler. Radiation dose ranged from 12-13.2 Gy in 6-11 fractions BID, per transplant protocol. Kidney blocks were delineated from standing AP/PA x-ray urogram and cut from cerrobend with a thickness of one-half value layer, decreasing the kidney dose by an estimated 50%. Baseline estimated glomerular filtration rate (eGFR) was compared with six weeks, three months, six months, and one year post HCT. A normal eGFR was defined as >60 mL/min/1.73m2. Of the 45 pts treated, 30 were alive at six months and 24 had one year follow up. Median follow up was 21 months (range 8-49). A decrease in eGFR <60 was most common at six weeks (5 pts, 17%) and three months (7 pts, 23%). At six months post HCT three of 28 pts (11%) with normal baseline kidney function had a decreased eGFR, which was acquired during the first three months post HCT. At one year, two of the three pts met criteria for CKD. The development of CKD in these pts is attributed to acute post HCT events, such as hypotension, infection, and medication adverse effect. Two pts had baseline CKD with a pre-treatment eGFR of 40 and 50. These pts experienced further decrease in eGFR by one year to 30 and 42, respectively. There were no de-novo decreases in eGFR to <60 at six months and one year, which represent the criteria for ARN. While this series is limited by number of pts and follow up, no pts developed a de-novo decrease in eGFR to <60 at six months or one year, indicating partial transmission kidney blocks may have decreased the risk of ARN. Pts have many risk factors for AKI and CKD in both the acute and long term period post HCT, but radiation nephropathy risk may be modifiable. This series demonstrates the feasibility of partial transmission kidney blocks.