Iron deficiency in non-dialysis chronic kidney disease

CASE PRESENTATION A 44-year-old African-American woman was evaluated in our clinic for hypertension and renal insufficiency. She had been diagnosed with hypertension 5 years earlier, and had recently been found to have an increased serum creatinine and more difficult to control blood pressure. After clinical evaluation, the renal disease was determined to be, most probably, a result of hypertensive nephrosclerosis. Her past medical history was otherwise unremarkable. Medications included atenolol 50 mg twice daily, valsartan 160 mg daily, hydrochlorothiazide 25 mg daily, and amlodipine 5 mg daily. The patient did not smoke or consume excessive alcohol; she worked as a secretary and has one daughter. There was a strong family history of hypertension. Review of systems was notable for fatigue and reduced libido. Physical examination revealed blood pressure 150/100 mm Hg and moderate obesity, but was otherwise unremarkable. She had a serum creatinine of 1.5 mg per 100 ml, hemoglobin (Hb) 10 g per 100 ml, with an estimated glomerular filtration rate of 42 ml/min. Her urinalysis was notable for trace protein and a bland sediment. The urine spot protein-to-creatinine ratio was 0.34. The patient was educated about chronic kidney disease, hypertension, and diet. Hydrochlorothiazide was discontinued, and furosemide 40 mg twice daily was started. Blood pressure improved to 135/90 mm Hg, at which time the dose of amlodipine was increased to 10 mg daily. Subsequently erythropoietin treatment was initiated once blood pressure was controlled. At this time, iron indices were serum ferritin 81 ng/ml and transferrin saturation 29%. The patient consented to take part in the CHOIR (Correction of Hemoglobin and Outcomes in Renal Insufficiency) study, an open label trial of weekly epoetin alfa treatment to raise Hb to a target of either 11.3 or 13.5 g per 100 ml.(1) The patient was randomized to the higher Hb target group. Treatment was initiated with epoetin alfa 10,000 U/week in the month of April in 2003. The initial response was brisk, with Hb increasing from 9.8 to 12.3 g per 100 ml (Figure 1). At that point, responsiveness waned and Hb did not reach the target. The dose of epoetin alfa was raised per protocol to 20,000 U/week (Figure 1). In addition, the patient was found to be iron deficient. Intravenous sodium ferric gluconate was administered at a dose of 250 mg for 4 weekly infusions. Iron indices improved and Hb rose to the target for approximately 8 weeks. Iron deficiency, however, redeveloped and Hb levels fell again to remain consistently below the target level. Renal function remained stable. Despite repeated intravenous iron treatment, iron deficiency persisted. The patient had been having excessively heavy menstrual flows, which she noted had been present for many months, and was advised to see a gynecologist. After several delays, gynecology evaluation was performed, and a diagnosis of excessive menstrual blood loss due to uterine leiomyomas (fibroids) was made. The patient was withdrawn from participation in the CHOIR study, but treatment with epoetin alfa at 20,000-40,000 U/week was continued. Treatment was initiated with the gonadotropin-releasing hormone agonist, leuprolide acetate. Within 2 months, the patient developed amenorrhea with a substantially reduced uterine size. With amenorrhea and oral iron therapy, iron indices improved and Hb rose to greater than 14 g per 100 ml. The dose of epoetin alfa was reduced to 10,000 U/week.