Bone Marrow Transplant Nephropathy: Radiation Nephritis Revisited

Cohen, Eric P.; Lawton, C.A.; Moulder, John E.

doi:10.1159/000188587

Cited by 96 publications

(77 citation statements)

References 32 publications

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“…11 The higher dose of TBI needs to be considered in interpreting our results because models of transplantation have shown that the renal insufficiency after BMT appears to be a form of radiation nephritis. 3 Degree of renal injury observed in our patients who were not shielded is unlikely to be seen in patients who receive 12 Gy TBI, and the importance of renal shielding or genotype might not be apparent in subjects irradiated to 12 Gy TBI or less.…”

Section: Discussionmentioning

confidence: 67%

“…A distinct syndrome of chronic renal failure after BMT termed 'bone marrow transplant nephropathy' has been described that consists of azotemia, disproportionate anemia, and hypertension. 2,3 This syndrome is thought to be due to either microvascular or renal parenchymal damage from the preparative regimen and in its most severe form resembles hemolytic uremic syndrome (HUS).Studies using animal models of BMT nephropathy have shown that angiotensin converting enzyme (ACE) inhibitors can effectively prevent and treat the syndrome. 4,5 This finding implicates the renin-angiotensin axis in the pathogenesis of the disorder.…”

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

Juckett

Cohen

Keever-Taylor

et al. 2001

Bone Marrow Transplant

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Summary:Chronic renal failure is an acknowledged late complication of BMT. It is related to the intensive chemotherapy, radiation and supporting medications. Polymorphism in the angiotensin converting enzyme (ACE) gene is associated with progression of nephropathy caused by diabetes and IgA nephropathy. We sought to determine whether ACE genotype and other clinical factors were associated with loss of renal function after BMT. We determined the genotype of 106 adult allogeneic BMT recipients, who received a similar preparative regimen, survived 1 year, and had assessment of renal function up to 3 years after BMT. We found that the distribution of genotypes was similar to the general population; 29%, 51%, and 20% for the DD, DI, and II genotypes, respectively. There was no statistical difference in patient survival between the three groups. Among all patients, the average creatinine clearance declined from 124 (95% CI 117, 131) to 89 (95% CI 78, 100) ml/min over the 36 months after BMT. Decline in renal function over time was less for patients with the DD compared to the II genotype (P = 0.040). Renal function in patients with the DD genotype was also better than those with the DI genotype, but this was of borderline statistical significance (P = 0.055). Renal shielding reduced decline in renal function compared to no shielding (P = 0.026). We conclude that the ACE genotype does not seem to influence survival, but the DD genotype may be protective against renal injury after BMT. Furthermore, we confirm that renal shielding during TBI reduces the renal injury after BMT. Bone Marrow Transplantation (2001) The late occurrence of chronic renal failure is a known complication of allogeneic bone marrow transplantation. 1 The combined effects of intensive radiation and chemotherapy are implicated in the pathogenesis of acute and chronic renal insufficiency. Factors contributing to acute renal failure include hypotension, sepsis and the administration of nephrotoxic medications such as aminoglycoside antibiotics, cyclosporine, tacrolimus and amphotericin. A distinct syndrome of chronic renal failure after BMT termed 'bone marrow transplant nephropathy' has been described that consists of azotemia, disproportionate anemia, and hypertension. 2,3 This syndrome is thought to be due to either microvascular or renal parenchymal damage from the preparative regimen and in its most severe form resembles hemolytic uremic syndrome (HUS).Studies using animal models of BMT nephropathy have shown that angiotensin converting enzyme (ACE) inhibitors can effectively prevent and treat the syndrome. 4,5 This finding implicates the renin-angiotensin axis in the pathogenesis of the disorder. ACE is responsible for the cleavage of angiotensin I to angiotensin II, which has potent effects on vascular tone, growth and repair. The ACE gene contains a polymorphism based on the presence or absence of a 287-base pair intron. 6 The presence of the intron has been termed the 'insertion' or 'I' allele, and the absence of the intron the 'deletion' or...

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Section: Discussionmentioning

confidence: 67%

mentioning

confidence: 99%

mentioning

confidence: 99%

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

Juckett

Cohen

Keever-Taylor

et al. 2001

Bone Marrow Transplant

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“…Late nephropathy with rapid deterioration of renal function can present acutely in association with haemolytic anaemia, while chronic onset may occur after gradual decline in kidney function. 32 Irradiation and in particular TBI in combination with immunosuppressive and supportive medication represent the main risk factors for patients who developed chronic renal impairment. 33 Miralbell et al 34 reported renal dysfunction after allogeneic HSCT strongly related to TBI dose and GvHD.…”

Section: Renal Complicationsmentioning

confidence: 99%

Non-endocrine late complications in children after allogeneic haematopoietic SCT

Faraci¹,

Békássy

Fazio³

et al. 2008

Bone Marrow Transplant

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“…[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]technique and compared using an extension of the lowed by syngeneic BMT. An additional 11 animals Kruskal-Wallis test.…”

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Noncontinuous use of angiotensin converting enzyme inhibitors in the treatment of experimental bone marrow transplant nephropathy

Moulder

Cohen

1997

Bone Marrow Transplant

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Summary:tors have been demonstrated in a rat syngeneic BMT model. More recently, an angiotensin II (AII) receptor antagonist has also been shown to be effective in the Angiotensin-converting enzyme (ACE) inhibitors can be used to prevent the development of radiation nephroprophylaxis of experimental BMT nephropathy. 17 To date, the experimental studies of prophylaxis of BMT pathy after BMT. In previous BMT nephropathy studies, ACE inhibitor therapy was started pre-BMT and nephropathy have used continuous treatment with ACE inhibitors or AII antagonists, with treatment starting before continued indefinitely. In preparation for clinical trials, studies were designed to determine whether effective the BMT conditioning regimen, and continuing indefinitely. [13][14][15][16][17] However, if these agents are to be used cliniprophylaxis could be achieved if ACE inhibitor therapy was started after engraftment, and to determine cally, it would be useful to know whether the start of drug therapy could be delayed until after engraftment. It would whether ACE inhibitors needed to be given indefinitely. The present studies in our rat syngeneic BMT model also be useful to know whether drug therapy would need to continue indefinitely. The answers to these questions showed that captopril therapy started 25 days post-BMT was as effective as therapy started prior to BMT.could also shed light on the mechanism(s) underlying the beneficial effects of ACE inhibitor and AII antagonist therWhen ACE inhibitor therapy was discontinued 28 weeks after BMT, the protective effect was not lost if apy against radiation nephropathy. 18 If therapy is effective when started after TBI, then it would establish that the adequate control of azotemia had been maintained for 26 weeks. If adequate control of azotemia was not maineffect was not an example of classical chemical radioprotection. 19 If therapy can be safely discontinued, then it tained for 26 weeks, BMT nephropathy progressed rapidly when ACE inhibitor therapy ended, and slowly would imply that the treatment is fundamentally altering the expression of radiation injury rather than delaying it. 18 when it was continued. Failure to control azotemia was a better predictor of renal failure than failure to controlTo answer these questions, two sets of studies were conducted in the rat syngeneic BMT model. In the first study, hypertension or proteinuria. Based on these preclinical studies, it would appear that ACE inhibitor therapy will animals started on captopril therapy at 25 days post-BMT were compared to animals that either started on captopril be effective in the prophylaxis of BMT nephropathy even if begun after engraftment, and that ACE inhibi-10 days pre-BMT, or given BMT without drug therapy. In the second study, animals were started on ACE inhibitor tors may not need to be given indefinitely.

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Bone Marrow Transplant Nephropathy: Radiation Nephritis Revisited

Cited by 96 publications

References 32 publications

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

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

Non-endocrine late complications in children after allogeneic haematopoietic SCT

Noncontinuous use of angiotensin converting enzyme inhibitors in the treatment of experimental bone marrow transplant nephropathy

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