Radiation Nephropathy Workup

Updated: Mar 22, 2021
  • Author: Jaya Kala, MD; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Approach Considerations

Basic tests in the assessment of radiation nephropathy include the following:

  • Urinalysis - Granular casts indicate renal parenchymal injury; red cell casts are not consistent with radiation nephropathy or bone marrow transplantation (BMT) nephropathy and instead suggest  acute glomerulonephritis.
  • Complete blood cell count  (CBC) - To evaluate the degree of anemia and/or thrombocytopenia. In BMT nephropathy, lower platelet counts correlate with a more rapid decline in kidney function; in less severe cases, the drop in the platelet count is transient.
  • Kidney function studies
  • Lactate dehydrogenase (LDH) - The degree of LDH elevation correlates with the rapidity of renal failure in BMT nephropathy. The increased LDH level in BMT nephropathy may be transient.
  • Potassium -  Hyperkalemia (serum potassium > 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. 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.

Proteinuria at non-nephrotic levels may be evident. It is difficult to delineate whether this is due to radiation exposure itself or a result of hypertension.

The severity of anemia is disproportionate to the degree of azotemia. This could be as a result of depletion of erythropoietin or glomerular capillary tuft damage leading to microangiopathic hemolytic anemia. [17]

Kidney function studies

Blood urea nitrogen (BUN) and serum creatinine should be measured to assess overall kidney function; the levels correlate with the glomerular filtration rate (GFR). The abbreviated Modification of Diet in Renal Disease (MDRD) formula may be used to estimate the GFR. [20]  The Cockcroft-Gault formula uses patient age and weight, along with serum creatinine, to  estimate the creatinine clearance, without a 24-hour urine collection. These formulas should be used only if the patient has a stable plasma creatinine level; otherwise, the Creatinine Clearance Estimate for Changing Serum Creatinine may be used. Neither the MDRD or the Cockcroft-Gault formula applies to patients with acute kidney injury.

Other laboratory studies

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

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 hypertension (blood pressure > 160/100 mm Hg).


Urine Protein Level

The protein-to-creatinine ratio provides an estimate of the amount of protein in the urine over a 24-hour period. 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. [21]


Imaging Studies

Ultrasonography helps in ruling out urinary tract obstruction. A reduction in kidney size occurs over time. The finding of smaller kidneys with increased echogenicity 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.

In a case report of radiation nephropathy, fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) showed an increase in FDG activity in portions of the kidney that had been previously irradiated. [22]

Some studies have shown that post-radiation scintigraphy in combination with biochemical measures may allow for early identification and assessment of patients who are at higher risk for developing clinical manifestations of radiation-induced kidney injury. [17]



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. [23]

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 acute kidney injury 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.


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 disease, with the need for renal replacement therapy such as dialysis or kidney transplantation. [15]

The graph of 100/plasma creatinine yields a number that varies directly with the GFR and is a fair estimate of the GFR. The graph of 100/plasma creatinine over 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.


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 - Glomerular filtration rate (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