Radiation Nephropathy Workup
- Author: Eric P Cohen, MD; Chief Editor: Vecihi Batuman, MD, FACP, FASN more...
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
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.
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.
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).
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.
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.
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.
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.
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.
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.
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 failure, with the need for renal replacement therapy, such as dialysis or kidney transplantation.
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.
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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