title: Retinoic acid may increase the risk of bone marrow transplant nephropathy.
abstract: Bone marrow transplant nephropathy (BMTN) classically presents more than 100 days after transplantation as an acute nephritis with hypertension, azotaemia and anemia that usually results in end stage renal failure (ESRF). The risk of developing BMTN may be greater with the use of more intensive chemotherapy and higher total body and tumor bed irradiation. Cis-retinoic acid (RA) may further increase the risk of developing BMTN. Here, we report the cases of two children who developed typical clinical and biochemical features of BMTN. They were both treated for stage IV neuroblastoma with chemotherapy, bone marrow transplant (BMT) conditioning that included total body irradiation and RA therapy after BMT, although the patient in case 1 had established renal insufficiency prior to the commencement of RA. Renal biopsy of these children showed classical BMTN histology, and the renal manifestations progressed quickly; the patient in case 1 became dialysis dependent by 1 year post-bone marrow transplant. Recently, RA has been added to the post-BMT therapy in children with stage IV neuroblastoma. The occurrence of BMTN in two children treated with RA in our unit is unlikely to be coincidental. Although RA has been shown to confer a significant survival advantage in this disease, animal studies and a previous case report have suggested it could increase the toxic effects of chemotherapy and renal irradiation. It is likely that RA contributed to the deterioration in renal function in these patients.
authors.affiliation: Department of Nephrology, Sydney Children's Hospital, Randwick, N.S.W., Australia.
authors.forename: Leigh
authors.initials: L
authors.lastname: Haysom
authors.forename: David S
authors.initials: DS
authors.lastname: Ziegler
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Cohn
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Rosenberg
authors.forename: Susan L
authors.initials: SL
authors.lastname: Carroll
authors.forename: Gad
authors.initials: G
authors.lastname: Kainer
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology* / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D011182:Postoperative Care; D013237:Stereoisomerism; D014212:Tretinoin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D014212:Tretinoin
references.citation: Int J Radiat Oncol Biol Phys. 1988 Jul;15(1):99-104
references.pmid: 2968967
references.citation: J Clin Oncol. 1995 Nov;13(11):2789-95
references.pmid: 7595740
references.citation: Radiology. 1978 Aug;128(2):491-5
references.pmid: 663265
references.citation: Int J Radiat Oncol Biol Phys. 1987 May;13(5):765-72
references.pmid: 3106272
references.citation: Int J Radiat Oncol Biol Phys. 2002 Nov 15;54(4):1165-73
references.pmid: 12419445
references.citation: Kidney Int. 1999 Aug;56(2):486-93
references.pmid: 10432387
references.citation: Bone Marrow Transplant. 2001 Feb;27(4):451-6
references.pmid: 11313676
references.citation: Acta Radiol Oncol. 1981;20(1):5-8
references.pmid: 6264743
references.citation: Radiat Res. 2002 Feb;157(2):199-203
references.pmid: 11835684
references.citation: Lancet. 1990 Oct 6;336(8719):850-4
references.pmid: 1976883
references.citation: J Lab Clin Med. 1999 Sep;134(3):283-91
references.pmid: 10482314
references.citation: Blood. 1988 Aug;72(2):451-5
references.pmid: 3042040
references.citation: Clin Nephrol. 1978 Aug;10(2):74-8
references.pmid: 699403
references.citation: Cancer Lett. 2003 Jul 18;197(1-2):185-92
references.pmid: 12880980
references.citation: Bone Marrow Transplant. 1997 Apr;19(7):729-35
references.pmid: 9156251
references.citation: Am J Med. 1976 Jan;60(1):127-37
references.pmid: 1251842
references.citation: J Clin Oncol. 1994 Dec;12(12):2607-13
references.pmid: 7527454
references.citation: Int J Radiat Oncol Biol Phys. 1995 Mar 30;31(5):1249-56
references.pmid: 7713786
references.citation: Pediatr Nephrol. 1999 Nov;13(9):755-8
references.pmid: 10603114
references.citation: Int J Radiat Oncol Biol Phys. 1994 Mar 1;28(4):883-9
references.pmid: 8138441
references.citation: N Engl J Med. 1990 Feb 15;322(7):417-21
references.pmid: 2300104
references.citation: Phys Med Biol. 1996 Nov;41(11):2307-26
references.pmid: 8938028
references.citation: J Lab Clin Med. 1994 Dec;124(6):761-5
references.pmid: 7798787
references.citation: N Engl J Med. 1999 Oct 14;341(16):1165-73
references.pmid: 10519894
references.citation: Curr Pharm Des. 2003;9(9):737-49
references.pmid: 12570791
references.citation: Bone Marrow Transplant. 2002 Jan;29(2):129-36
references.pmid: 11850707
references.citation: Nephron. 1993;64(4):626-35
references.pmid: 8366991
references.citation: Kidney Int. 1989 Jun;35(6):1336-44
references.pmid: 2671466
references.citation: Bone Marrow Transplant. 1991 May;7(5):383-8
references.pmid: 2070148
references.citation: Arch Physiol Biochem. 1996;104(2):200-6
references.pmid: 8818205