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Kidney and Ureter

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ALERT • Adverse Late Effects of Cancer Treatment

Part of the book series: Medical Radiology ((Med Radiol Radiat Oncol))

Abstract

• The kidneys are dose-limiting for radiation therapy of cancers of the upper abdomen, as well as for conditions treated with total body irradiation and bone marrow transplant or hematopoietic stem cell transplant.

• The architecture of the kidneys can be considered as subunits (i.e. nephrons) that are predominantly arranged “in parallel”, but with some serial function.

• The nephron is the basic structural and functional unit of the kidneys. It depends on a complex vascular system.

• The major target for injury appears to be the arteriolar-glomerular area rather than the tubular epithelium, as the earliest cellular feature of RT-induced kidney injury is glomerular endothelial cell injury.

• The kidneys maintain the homeostasis of body fluids by filtering metabolites, including the urea and fixed acid of protein catabolism.

• Glomerular filtration rate (GFR) measurements may help to adjust the dosing of cytotoxic agents, and accurate chemotherapy dosing may reduce side effects of the cytotoxic agents, all the while retaining their benefit.

• Intra-renal TGF-beta is elevated in experimental radiation nephropathy, but it is not clear if it results from injury or initiates it.

• The bone marrow transplant (BMT) nephropathy syndrome, has been defined as azotemia (doubling of baseline serum creatinine level or a >50 % decrease in the glomerular filtration rate (GFR)), hypertension, and anemia after transplant, and it occurs ≈8–12 months post-transplant.

• The time from bilateral kidney irradiation to clinical symptoms of radiation nephropathy can range from 1–9 months (in the acute presentation) to 18 years + (in the chronic presentation) of radiation nephropathy.

• Total dose associated with a 5 % risk of injury at 5 years, TD5/5, of 18–23 Gy, and a total dose associated with a 50 % risk of injury at 5 years, TD50/5, of 28 Gy, in 0.5–1.25 Gy per fraction.

• TBI dose appears to be related to risk of renal toxicity post hematopoietic stem cell transplant.

• Unilateral kidney irradiation may be followed by injury, as shown by Thompson et al. who observed a dose response for kidney atrophy and clinical kidney toxicity many years following unilateral kidney RT (Thompson et al. 1971). The effective dose associated with scintigraphic changes in 50 % of the patients (ED50) was 27 Gy when 10 % of the bilateral kidney volume was irradiated. Neonates appear to have an increased sensitivity to RT. Doses of 12–14 Gy at 1.25–1.5 Gy per fraction to the entire neonate kidney have been associated with a decreased GFR (Peschel et al. 1981).

• The therapeutic efficacy of radiolabeled antibody fragments can be limited by renal toxicity, particularly when the kidney is the major route of extraction from the circulation.

• Ureteric strictures following irradiation were first reported in 1934 following pelvic irradiation and radium brachytherapy for gynecological malignancies (Everett 1934).

• Chemotherapy related injury may manifest itself as acute renal failure (ARF), chronic renal failure, or specific tubular defects.

• Animal models of BMT nephropathy have shown that angiotensin converting enzyme (ACE) inhibitors, dexamethasone, or acetylsalicylic acid can prevent and treat chronic renal failure (Moulder et al. 2007); (Verheij et al. 1995; Cohen et al. 1997; Cohen et al. 2007); (Moulder et al. 1987, 1998a, b).

• In chronic kidney disease, a reduction in renal workload by low protein diet, and salt restriction may delay the progression to renal failure.

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Abbreviations

(ACE):

Angiotensin converting enzyme

(ARF):

Acute renal failure

(BMT):

Bone marrow transplant

(CrCl):

Clearance of creatinine

(DVH):

Dose–volume histogram

(GFR):

Glomerular filtration rate

(HSCT):

Hematopoietic stem cell transplant

(HUS):

Hemolytic uremic syndrome

(NTCP):

Normal tissue complication probability

(NT):

Nephrotoxic

(RT):

Radiation therapy

(TBI):

Total body irradiation

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Acknowledgments

This work was supported in part by a grant from the National Institutes of Health, USA, NIH/NIAID U19 AI067734 (John Moulder, PI, Eric Cohen, co-investigator). The authors appreciate the thoughtful comments regarding this chapter from Dr. Jolie Ringash, Dr. Zahra Kassam, and Dr. Charles Cho, staff radiation oncologists, and Dr. Mark Lee radiation oncology fellow from the Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto.

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Authors and Affiliations

  1. Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, 610 University Avenue, Toronto, ON, M5G 2M9, Canada

    Laura A. Dawson

  2. Waterford Regional Hospital, Waterford, Ireland

    Anne Horgan

  3. Professor of Medicine, Nephrology Fellowship Director, Medical College of Wisconsin, Milwaukee, USA

    Eric P. Cohen

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  1. Laura A. Dawson
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  2. Anne Horgan
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  3. Eric P. Cohen
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Correspondence to Anne Horgan .

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Editors and Affiliations

  1. Dept. Radiation Oncology, University of Rochester Medical Center James P. Wilmot Cancer Ctr., Rochester, New York, USA

    Philip Rubin

  2. Department of Radiation Oncology, University of Rochester Medical Center James P. Wilmot Cancer Ctr., Rochester, New York, USA

    Louis S. Constine

  3. Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina, USA

    Lawrence B. Marks

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Dawson, L.A., Horgan, A., Cohen, E.P. (2014). Kidney and Ureter. In: Rubin, P., Constine, L., Marks, L. (eds) ALERT • Adverse Late Effects of Cancer Treatment. Medical Radiology(). Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-75863-1_17

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  • DOI: https://doi.org/10.1007/978-3-540-75863-1_17

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