Radiation Nephropathy Medication

Control of hypertension and treatment of anemia are necessary. In BMT nephropathy, the occurrence of hyperkalemia requires additional attention. For the control of hypertension, ACE inhibitors are preferred, but they may raise the serum potassium level and should be avoided if the patient is hyperkalemic. Other antihypertensives, such as calcium channel blockers and diuretics, may be used to control blood pressure. Experience at the author’s center is that 75% of patients with radiation nephropathy require diuretics for control of their blood pressure.

Class Summary

These agents reduce the systemic arterial blood pressure, reducing injury caused by elevated blood pressure. They may not only reduce cardiovascular risk but also slow progression of renal failure. ACE inhibitors may also slow progression of renal failure by lowering intraglomerular pressure or other intrarenal mechanisms.

A dry cough can occur in about 5% of subjects taking ACE inhibitors. If the cough occurs with one ACE inhibitor, it is likely to occur with another. If a cough develops, a reasonable substitute for an ACE inhibitor is an ARB, such as losartan, valsartan, or candesartan.

Captopril

Captopril, a competitive ACE inhibitor, prevents the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, increasing levels of plasma renin and reducing angiotensin II levels and aldosterone secretion. It has been clinically used for more than 30 years and is effective in experimental radiation nephropathy. Captopril may slow the progression of renal failure by lowering intraglomerular pressure or other intrarenal mechanisms.

Enalapril (Vasotec)

This competitive ACE inhibitor also reduces angiotensin II levels, decreasing aldosterone secretion. The drug lowers systemic arterial blood pressure, reducing injury caused by elevated blood pressure. It may slow the progression of renal failure by lowering intraglomerular pressure or other intrarenal mechanisms. Enalapril may be used every day or twice per day, which may improve compliance in comparison with a 3-time-per-day medication, such as captopril.

Class Summary

ARBs antagonize the action of angiotensin II at its type 1 receptor, reducing systemic arterial blood pressure and blunting the intrarenal effect of angiotensin II. If ACE inhibitors cause cough, ARBs may be substituted.

Losartan (Cozaar)

Losartan is the prototype ARB. It is specific for the type 1, as opposed to type 2, angiotensin receptor. It may induce more complete inhibition of the renin-angiotensin system than do ACE inhibitors. Losartan does not appear to affect bradykinin and is less likely to cause a cough or angioedema. One can use it in patients who do not tolerate ACE inhibitors.

Valsartan (Diovan)

Valsartan also directly antagonizes angiotensin II receptors. Like losartan, it displaces angiotensin II from the AT1 receptor and may lower blood pressure by antagonizing AT1-induced vasoconstriction, aldosterone release, catecholamine release, arginine vasopressin release, water intake, and hypertrophic responses. Valsartan may induce more complete inhibition of the renin-angiotensin system than do ACE inhibitors. It does not affect bradykinin and is unlikely likely to cause a cough or angioedema. Valsartan can be used in patients who do not tolerate ACE inhibitors.

Class Summary

Antihypertensive agents other than or in addition to ACE inhibitors and ARBs may be needed for blood pressure control in many subjects with hypertension and chronic renal failure. The same is true for subjects with radiation nephropathy. No evidence indicates that one type of calcium channel blocker is preferred over another for radiation nephropathy. However, one should avoid verapamil, because the use of this drug in a subject with hyperkalemia may cause atrial arrest.

Nifedipine (Procardia, Adalat, Nifedical XL)

Like other calcium channel blockers, nifedipine causes peripheral arterial vasodilation by inhibiting calcium influx across vascular smooth-muscle cell membranes. Long-acting formulations are used for control of blood pressure.

Class Summary

Hyperkalemia may occur in patients with BMT nephropathy, whether or not they are simultaneously taking ACE inhibitors or ARBs. For life-threatening hyperkalemia (plasma K >6 mmol/L and/or electrocardiographic changes), emergency measures, such as IV glucose and insulin, are needed. For persistent, lesser degrees of hyperkalemia, a cation exchange resin may be needed to remove potassium by means of the gut.

Sodium polystyrene sulfonate (Kayexalate, Klonex, Kalexate)

Sodium polystyrene sulfonate is given by mouth or retention enema. It exchanges approximately 2 sodium atoms for 1 potassium atom; the potassium is then lost in the feces.

Class Summary

Impaired potassium excretion in BMT nephropathy may be associated with low blood levels of aldosterone. In other causes of chronic renal failure with such aberrant potassium metabolism, use of a synthetic mineralocorticoid has been helpful.

Fludrocortisone

Fludrocortisone mimics the action of aldosterone, promoting sodium retention and potassium excretion.

Class Summary

Anemia may occur in radiation nephropathy and BMT nephropathy, which has been associated with low blood levels of endogenous erythropoietin. Treatment of anemia with exogenous erythropoietin may relieve symptoms of anemia.

Epoetin (Epogen, Procrit)

This glycoprotein is a recombinant human erythropoietin (glycoprotein with 165 amino acids). It stimulates bone marrow red blood cell (RBC) production. It is widely used in subjects who require chronic dialysis for end-stage renal disease. Epoetin is given intravenously or by subcutaneous (SC) injection.

Darbepoetin alfa (Aranesp)

This is an erythropoiesis-stimulating protein that is closely related to erythropoietin. Its mechanism of action is similar to that of endogenous erythropoietin, which interacts with stem cells to increase RBC production. Darbepoetin alfa differs from epoetin alfa (recombinant human erythropoietin) in that it contains 5 N-linked oligosaccharide chains, whereas epoetin alfa contains 3. Darbepoetin also has a longer half-life than epoetin alfa; it may be administered weekly or biweekly.

Class Summary

Control of hypertension in radiation nephropathy and most chronic renal diseases requires the use of a diuretic. This is the clinical correlate of impaired natriuresis that exists in most forms of experimental hypertension. Additionally, diuretics facilitate potassium excretion.

Hydrochlorothiazide (Microzide)

Hydrochlorothiazide (HCTZ) acts on the distal nephron to impair sodium and chloride reabsorption, thus enhancing sodium excretion. It has been in use for more than 40 years and is an important agent for the treatment of essential hypertension.

Furosemide (Lasix)

Furosemide acts on the thick ascending limb of loop of Henle to enhance sodium, potassium, and chloride and water excretion. It is more potent than HCTZ and may be required for the control of fluid retention in subjects with impaired renal function.