Angiotensin-converting-enzyme inhibition therapy in altitude polycythaemia: a prospective randomised trial

Background Angiotensin-converting-enzyme (ACE) inhibitors reduce packed cell volume and haemoglobin concentration in polycythaemia that follows renal transplantation, which, like altitude polycythaemia, is an erythropoietin-dependent form of polycythaemia. We aimed to establish the effect of ACE-inhibitor treatment in people with altitude polycythaemia. Methods We did a prospective randomised study in 26 people with altitude polycythaemia (packed cell volume greater than or equal to55%) and 24-h rate of urinary protein excretion greater than 150 mg, who had been referred to the Renal Disease Project in La Paz, Bolivia. 13 participants were assigned 5 mg/day enalapril for 2 years (study group), and 13 no treatment (controls). Blood pressure, packed cell volume and haemoglobin concentration, proteinuria, and renal function were compared by intention-to-treat analyses. Findings Baseline packed cell volume and haemoglobin concentration were positively correlated with bodyweight (p=0.02), systolic (p=0.01) and diastolic (p=0.04) blood pressure, serum creatinine (p=0.0009), blood urea (p=0.008), and proteinuria (p=0.003). Systolic and diastolic blood pressure remained stable in the study group, but increased in controls. In study patients, mean (SD) packed cell volume, haemoglobin concentration, and proteinuria fell from 63.5% (4.9) to 56.8% (4.1), p<0.0001; 207 (18) to 164 g/L (13), p<0.0001; and from 358.6 (260.3) to 247.7 mg/24-h (208.2), p<0.002, respectively, but did not change significantly in controls. At 12 and 24 months of follow-up, packed cell volume, haemoglobin concentration, and proteinuria differed significantly between the groups (p<0.0001 for each comparison). In study patients, follow-up changes in packed cell volume (r=0.88, p<0.0001) or haemoglobin concentration (r = 0.83, p<0.0001) and proteinuria were strongly correlated. Enalapril was well tolerated by all patients. Interpretation ACE-inhibition therapy effectively and safely ameliorates altitude polycythaemia and reduces proteinuria.