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Radiation Nephropathy Workup

  • Author: Eric P Cohen, MD; Chief Editor: Vecihi Batuman, MD, FACP, FASN  more...
 
Updated: Dec 01, 2015
 

Approach Considerations

Various laboratory studies may be useful in the differential diagnosis of renal failure with nephrotic-range proteinuria and should be ordered according to the clinical presentation. These studies include the following:

  • Serum complement testing
  • Antinuclear antibody measurement
  • Antineutrophil cytoplasmic antibody measurement
  • Hepatitis panel
  • Protein electrophoreses

Urinalysis

Urinalysis results may show renal parenchymal injury by showing granular casts. The presence of red cell casts is not consistent with radiation nephropathy or BMT nephropathy and instead suggests acute glomerulonephritis.

CBC count

A complete blood count (CBC) helps to evaluate the degree of anemia and/or thrombocytopenia. In BMT nephropathy, lower platelet counts correlate with a more rapid decline in renal function. In less severe cases, the drop in the platelet count is transient.

Plasma LDH level

This level has been correlated with the rapidity of renal failure in BMT nephropathy. The increased LDH level in BMT nephropathy may be transient.

Plasma potassium level

Hyperkalemia (serum [K] >5.5 mmol/L) may occur in BMT nephropathy, even in subjects not taking angiotensin-converting enzyme (ACE) inhibitors, angiotensin II-receptor blockers (ARBs), or cyclosporine A. Further studies may show that the fractional excretion of potassium is lower than expected for the degree of azotemia. In addition, the plasma aldosterone level may be low.

Kidney biopsy

Although not necessary in every case, kidney biopsy allows histologic confirmation of the diagnosis. Biopsy can be performed percutaneously or transvenously; it may be associated with bleeding complications in cases of thrombocytopenia (platelet count < 100,000/µL) or if blood pressure is high (>160/100 mm Hg).

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BUN and Serum Creatinine Levels

Blood urea nitrogen (BUN) and serum creatinine tests help in assessing overall kidney function and are correlated with the glomerular filtration rate (GFR). The abbreviated Modification of Diet in Renal Disease (MDRD) formula may be used to estimate the GFR.[14]

By using patient age and weight, the Cockcroft-Gault formula enables calculation of the creatinine clearance from the plasma creatinine, without a 24-hour urine collection. These formulas should be used only if the patient has a stable plasma creatinine level. Neither formula applies to patients with acute renal failure.

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Urine Protein Level

The protein-to-creatinine ratio provides an estimate of the amount of protein in the urine over a 24-hour period. The values help in assessing the degree of proteinuria. A 24-hour urine protein value higher than 3 g or more than 2 g per gram of urinary creatinine is in the nephrotic range.

Nephrotic-range proteinuria may suggest a diagnosis other than radiation nephropathy or BMT nephropathy. For instance, focal glomerulosclerosis can occur in subjects who have undergone BMT and then treatment with pamidronate. In these cases, the urine protein excretion may be high, even as high as 10 g/d.[15]

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Imaging Studies

Ultrasonography helps in ruling out urinary tract obstruction. A reduction in kidney size occurs over time. Images show smaller kidneys with increased echogenicity, and that is consistent with chronic radiation nephropathy, although it could be seen in many chronic progressive kidney diseases.

Long-standing or severe hypertension may cause cardiac enlargement with left ventricular hypertrophy, which can be seen on chest radiographs. With advanced renal failure and fluid retention, pleural effusions and/or interstitial edema may be present, which can also be seen on radiographs.

One case using FDG PET/CT showed an increase in FDG activity in portions of the kidney that had been previously irradiated.[16]

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Histologic Findings

In classic radiation nephropathy, arterial and arteriolar thickening is present, and arteriolar fibrinoid necrosis and ischemic and sclerotic glomerular changes are possible. Interstitial fibrosis is also present. Early descriptions of radiation nephropathy note glomerular hypocellularity and cellular degeneration. Electron microscopy shows endothelial degeneration and subendothelial expansion by electron-lucent material.[17]

In BMT nephropathy (see the image below), glomerular mesangiolysis, or loss of mesangial cells and rarefaction of the mesangial matrix, develops. Tubular atrophy and interstitial fibrosis may be present. Arteriolar fibrinoid necrosis has been described. As in classic radiation nephropathy, electron microscopy shows subendothelial expansion by electron-lucent material and endothelial degeneration. A similar appearance is described in cases of renal failure that occur after radioisotope internal radiotherapy.

Photomicrograph of a kidney-biopsy sample in a cas Photomicrograph of a kidney-biopsy sample in a case of nephropathy associated with bone marrow transplantation (periodic acid-Schiff stain). A glomerulus is in the center and is relatively hypocellular. Increased mesangial matrix is present. The glomerular basement membranes are not thickened; in some places, however, they are separated from the capillary lumens by a low-density, matrixlike material. Interstitial fibrosis separates the tubules from each other. Arteriolar thickening and arteriolar hyalin are present.

Proliferative crescentic glomerulonephritis has been reported as a rare, late complication of BMT. Kidney biopsy shows glomerular hypercellularity with crescent formation. This type of nephritis does not appear to be caused by irradiation.

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Rate of Kidney Function Loss

An estimate of the rate of kidney function loss can be made by graphing the reciprocal of the plasma creatinine versus time. The X intercept on the graph is a guide to when the patient will have reached end-stage renal failure, with the need for renal replacement therapy, such as dialysis or kidney transplantation.[10]

The graph of 100/plasma creatinine yields a number that varies directly with the GFR and that is a fair estimate of the GFR. The graph of 100/plasma creatinine versus time in BMT nephropathy may be biphasic (as seen in the graph below), with a rapid phase followed by a slower phase. Such graphs can be made by using spreadsheet programs, such as Microsoft Excel. Some clinical laboratories may report results on computer programs that allow easy portrayal of the laboratory data as a graph.

Evolution of the glomerular filtration rate (GFR) Evolution of the glomerular filtration rate (GFR) versus time in a case of nephropathy related to bone marrow transplantation (BMT). GFR may be approximated as 100/plasma creatinine on the Y axis and graphed versus time on the X axis. As is true in many cases of BMT nephropathy, the evolution appears to be biphasic, with an initial rapid decline in GFR, then a slower plateau phase. The patient whose data are shown here ultimately underwent kidney transplantation.
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Staging

In terms of kidney function, the stages of radiation nephropathy are the same as those of all chronic kidney diseases. These stages are as follows:

  • Stage I - GFR 90 mL/min or better, but injury present
  • Stage II - GFR 60-89 mL/min
  • Stage III - GFR 30-59 mL/min
  • Stage IV - GFR 15-29 mL/min
  • Stage V - GFR < 15 mL/min or dialysis needed
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Contributor Information and Disclosures
Author

Eric P Cohen, MD Professor, Department of Medicine, Division of Nephrology, University of Maryland School of Medicine; Nephrology Section Chief, Baltimore Veterans Affairs Hospital

Eric P Cohen, MD is a member of the following medical societies: American Society of Nephrology, Central Society for Clinical and Translational Research, International Society of Nephrology, Radiation Research Society, Société Francophone de Dialyse

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Ajay K Singh, MB, MRCP, MBA Associate Professor of Medicine, Harvard Medical School; Director of Dialysis, Renal Division, Brigham and Women's Hospital; Director, Brigham/Falkner Dialysis Unit, Faulkner Hospital

Disclosure: Nothing to disclose.

Chief Editor

Vecihi Batuman, MD, FACP, FASN Huberwald Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Renal Section, Southeast Louisiana Veterans Health Care System

Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, International Society of Nephrology

Disclosure: Nothing to disclose.

Additional Contributors

Laura Lyngby Mulloy, DO, FACP Professor of Medicine, Chief, Section of Nephrology, Hypertension, and Transplantation Medicine, Glover/Mealing Eminent Scholar Chair in Immunology, Medical College of Georgia, Georgia Regents University

Disclosure: Nothing to disclose.

References
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  2. Cohen EP. Radiation nephropathy after bone marrow transplantation. Kidney Int. 2000 Aug. 58(2):903-18. [Medline].

  3. Cohen EP, Moulder JE, Robbins ME. Radiation nephropathy caused by yttrium 90. Lancet. 2001 Sep 29. 358(9287):1102-3. [Medline].

  4. Sera N, Hida A, Imaizumi M, Nakashima E, Akahoshi M. The association between chronic kidney disease and cardiovascular disease risk factors in atomic bomb survivors. Radiat Res. 2013 Jan. 179(1):46-52. [Medline].

  5. Cohen EP, Robbins ME. Radiation nephropathy. Semin Nephrol. 2003 Sep. 23(5):486-99. [Medline].

  6. Moll S, Nickeleit V, Mueller-Brand J, et al. A new cause of renal thrombotic microangiopathy: yttrium 90-DOTATOC internal radiotherapy. Am J Kidney Dis. 2001 Apr. 37(4):847-51. [Medline].

  7. Giralt S, Bensinger W, Goodman M, et al. 166Ho-DOTMP plus melphalan followed by peripheral blood stem cell transplantation in patients with multiple myeloma: results of two phase 1/2 trials. Blood. 2003 Oct 1. 102(7):2684-91. [Medline].

  8. Cohen EP, Drobyski WR, Moulder JE. Significant increase in end-stage renal disease after hematopoietic stem cell transplantation. Bone Marrow Transplant. 2007 May. 39(9):571-2. [Medline].

  9. Akasheh M, Priyanath A, Pello N, et al. Accelerated atherosclerosis in a patient with post-BMT nephropathy. Bone Marrow Transplant. 1999 Jan. 23(2):199. [Medline].

  10. Cohen EP, Piering WF, Kabler-Babbitt C, Moulder JE. End-stage renal disease (ESRD) after bone marrow transplantation: poor survival compared to other causes of ESRD. Nephron. 1998 Aug. 79(4):408-12. [Medline].

  11. Antignac C, Gubler MC, Leverger G, Broyer M, Habib R. Delayed renal failure with extensive mesangiolysis following bone marrow transplantation. Kidney Int. 1989 Jun. 35(6):1336-44. [Medline].

  12. Bernauer W, Gratwohl A, Keller A, Daicker B. Microvasculopathy in the ocular fundus after bone marrow transplantation. Ann Intern Med. 1991 Dec 15. 115(12):925-30. [Medline].

  13. Cohen EP, Pais P, Moulder JE. Chronic kidney disease after hematopoietic stem cell transplantation. Semin Nephrol. 2010 Nov. 30(6):627-34. [Medline]. [Full Text].

  14. Stevens LA, Coresh J, Greene T, et al. Assessing kidney function--measured and estimated glomerular filtration rate. N Engl J Med. 2006 Jun 8. 354(23):2473-83. [Medline].

  15. Markowitz GS, Appel GB, Fine PL, et al. Collapsing focal segmental glomerulosclerosis following treatment with high-dose pamidronate. J Am Soc Nephrol. 2001 Jun. 12(6):1164-72. [Medline].

  16. Choi HJ, Shim H, Hyun H, Gerbaudo VH, Kim CK. FDG PET/CT Appearance of Radiation Nephritis. Clin Nucl Med. 2015 Nov 11. [Medline].

  17. Keane WF, Crosson JT, Staley NA, et al. Radiation-induced renal disease. A clinicopathologic study. Am J Med. 1976 Jan. 60(1):127-37. [Medline].

  18. Choi KL, Bakris GL. Hypertension treatment guidelines: practical implications. Semin Nephrol. 2005 Jul. 25(4):198-209. [Medline].

  19. Cohen EP, Hussain S, Moulder JE. Successful treatment of radiation nephropathy with angiotensin II blockade. Int J Radiat Oncol Biol Phys. 2003 Jan 1. 55(1):190-3. [Medline].

  20. Moulder JE, Fish BL, Cohen EP. Radiation nephropathy is treatable with an angiotensin converting enzyme inhibitor or an angiotensin II type-1 (AT1) receptor antagonist. Radiother Oncol. 1998 Mar. 46(3):307-15. [Medline].

  21. Cohen EP, Irving AA, Drobyski WR, et al. Captopril to mitigate chronic renal failure after hematopoietic stem cell transplantation: a randomized controlled trial. Int J Radiat Oncol Biol Phys. 2008 Apr 1. 70(5):1546-51. [Medline].

  22. Sarode R, McFarland JG, Flomenberg N, et al. Therapeutic plasma exchange does not appear to be effective in the management of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome following bone marrow transplantation. Bone Marrow Transplant. 1995 Aug. 16(2):271-5. [Medline].

 
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Evolution of the glomerular filtration rate (GFR) versus time in a case of nephropathy related to bone marrow transplantation (BMT). GFR may be approximated as 100/plasma creatinine on the Y axis and graphed versus time on the X axis. As is true in many cases of BMT nephropathy, the evolution appears to be biphasic, with an initial rapid decline in GFR, then a slower plateau phase. The patient whose data are shown here ultimately underwent kidney transplantation.
Photomicrograph of a kidney-biopsy sample in a case of nephropathy associated with bone marrow transplantation (periodic acid-Schiff stain). A glomerulus is in the center and is relatively hypocellular. Increased mesangial matrix is present. The glomerular basement membranes are not thickened; in some places, however, they are separated from the capillary lumens by a low-density, matrixlike material. Interstitial fibrosis separates the tubules from each other. Arteriolar thickening and arteriolar hyalin are present.
 
 
 
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