A Prospective, Randomized, Open Labeled Crossover Trial of Fosinopril and Theophylline in Post Renal Transplant Erythrocytosis

Abstract

Angiotensin converting enzyme inhibitors (ACEI) and theophylline have been reported to decrease the elevated hemoglobin (Hgb) and hematocrit (Hct) levels in the renal transplant recipients with erythrocytosis. We conducted a prospective randomized, open labeled, crossover trial with theophylline, and an ACEI, fosinopril in nine stable renal transplant recipients with erythrocytosis. Aim of the study was to determine and compare the efficacy of these medications in stable renal transplant patients. At three months, compared to baseline, fosinopril significantly reduced the elevated hemoglobin (Hgb 17.2 +/- 0.6 vs. 14.9 +/- 1.4 gm/dL, p = 0.0023), and hematocrit levels (Hct 51.3 +/- 2.4 vs. 43.7 +/- 4.6%, p = 0.003). In contrast theophylline therapy was associated with a non-significant rise in hemoglobin (17.4 +/- 0.7 vs. 18.1 +/- 0.9gm/dL, p > 0.05) and hematocrit (52.4 +/- 2.7 vs. 54.7 +/- 3.9%, p > 0.05). With fosinopril compared to theophylline, there was a significant difference in the change in hemoglobin (baseline to three months 2.8 +/- 1.7 vs. -0.7 +/- 0.69 gm/dL respectively, p = 0.017), and the change in hematocrit (baseline to three months 9 +/- 6 vs. -2.3 +/- 2.7% respectively, p = 0.027). Four patients (44.4%) did not tolerate theophylline and did not complete the theophylline arm. To conclude, in our study, fosinopril effectively decreased the elevated hemoglobin and hematocrit in patients with post transplant erythrocytosis, and was superior to theophylline, while theophylline was ineffective and poorly tolerated in this condition.

Special Issue: KDIGO Clinical Practice Guideline for the Care of Kidney Transplant Recipients

“…Theophylline has been found to be useful in the transplant population with dramatic absolute reductions in hematocrit of 8–12% (798,799). However, several trials have found that ACE‐Is were superior when compared directly to theophylline (800–802). In the study by Trivedi et al, the hematocrit fell by 7.6% in the ACE‐I arm (fosinipril, n = 9) and did not change significantly (rose by 2.3%) in the theophylline arm (n = 5) (802).…”

Antihypertensive Medications and Anemia

“…In addition, the studies of Yildiz and associates 50 have demonstrated a greater decrease in hemoglobin concentration with enalapril than with losartan; however, on discontinuation of therapy, relapse occurred more rapidly in those who received enalapril. Unless contraindications to their use exist, ACE inhibitors should remain the preferred compounds for suppression of erythropoiesis when such therapy is warranted 51 …”

“…unless contraindications to their use exist, aCe inhibitors should remain the preferred compounds for suppression of erythropoiesis when such therapy is warranted. 51 HeARt FAiluRe the clinical relevance of aCe inhibitor-related anemia is difficult to ascertain in the Hf patient, although they appear to dose-dependently produce anemia in Hf. 52 at the least, it is one of several contributing factors to the low-grade anemia observed in many Hf patients.…”

Post-transplant erythrocytosis refractory to ACE inhibitors and angiotensin receptor blockers

“…A recent randomised cross-over trial comparing fosinopril and theophylline demonstrated that fosinopril was superior to theophylline in terms of controlling hct 3434. Another therapeutic option that has been explored is ketanserin, a 5HT2 receptor antagonist 36.…”