Efficacy of losartan in the treatment of erythrocytosis in a young adult with CRF

We report a 25-year-old man who was born with bilateral hydroureteronephrosis. He was referred to the pediatric nephrology service in 1997 at 20 years of age for management of proteinuria and a declining glomerular filtration rate (GFR). At the time of referral, the patient was in good health. His height was 173.5 cm (33%), weight 80.9 kg (81%), and blood pressure (BP) 128/ 71 mmHg. Laboratory testing revealed hemoglobin 16.2 g/dl, creatinine 1.6 mg/dl, calculated GFR 76 ml/ min per 1.73 m2 [1], and a protein/creatinine (Up/c) ratio of 3.7 in an early morning urine specimen. He was started on the angiotensin converting enzyme inhibitor (ACEI) lisinopril 10 mg daily and his Up/c fell to 0.4. Over the next 5 years, he gradually developed erythrocytosis, with a hemoglobin level that rose from 15.8 to 19.6 g/dl. His serum creatinine concentration remained at 1.6 mg/dl, but his Up/c increased to 1.9, and he had systolic hypertension (BP 142/65 mmHg). In June 2003, at the age of 25 years, magnetic resonance imaging showed massive cystic changes in both kidneys, with small areas of remaining normal renal parenchyma. His lisinopril dose had been stable at 15 mg daily for 16 months. After evaluation by a hematologist for erythrocytosis, the patient was placed on losartan in addition to lisinopril. The response to this treatment is summarized in Table 1. In this case report, we show that inhibition of the renin-angiotensin system modulated erythrocytosis prior to kidney transplantation in a young adult with obstructive uropathy. The addition of an angiotensin II type 1 receptor blocker (ARB) was more effective than prior treatment with an ACEI alone. Several studies have documented a benefit of either ACEI or ARB in patients with post-transplant erythrocytosis [2, 3, 4]. We are aware of only one previous study demonstrating the benefit of ACEI in adult polycythemic patients who retained their native kidneys [5]. In a randomized study, Yildiz et al. [4] showed that enalapril caused a greater decrease in hemoglobin levels but a shorter time to relapse after discontinuation of the medication, compared with losartan in patients with posttransplantation erythrocytosis. They concluded that the two medications act through different mechanisms. Our case report is consistent with this proposal. However, since the ACEI was not discontinued, it is possible that the improvement following addition of losartan was secondary to an additive effect of the two medications, as opposed to a distinct pathway. The mechanism by which blockade of the reninangiotensin axis ameliorates erythrocytosis is a subject of debate. Some [2, 3], but not all [5], studies show a sustained decrease in erythropoietin levels in treated patients that parallels the fall in hemoglobin concentration. An alternative mechanism of action for losartan may be blockade of angiotensin II receptors on erythroid precursors [2]. Our data demonstrating a decrease in erythropoietin levels after initiation of losartan are consistent with a direct drug-mediated inhibition of erythropoietin secretion. The patient tolerated the use of both drugs without a decrement in kidney function or hyperkalemia. Moreover, M. L. Stoll · B. G. Gauthier · M. Vergara · R. Frank · H. Trachtman Department of Pediatrics, Division of Nephrology, Schneider Children’s Hospital of the North Shore–Long Island Jewish Health System, New Hyde Park, New York, USA