Anemia In Renal Transplant Recipients Research Articles

Congestive heart failure in renal transplant recipients: risk factors, outcomes, and relationship with ischemic heart disease.

Cardiovascular disease (CVD) is the major cause of death in renal transplant recipients (RTR). Several cohort studies have examined CVD in RTR, but none have addressed the development of congestive heart failure (CHF). CHF would hypothetically be a frequent and prognostically important event in RTR. A retrolective cohort study was, therefore, conducted in two Canadian centers to describe the incidence, risk factors for, and interrelationships between de novo CHF, de novo ischemic heart disease (IHD), and mortality in 638 consecutive adult RTR who were free of cardiac disease at 1 yr posttransplant. Detailed clinic and hospital records were available for 99% of patients. Median follow-up was 7 yr (range, 1 to 28 yr). De novo CHF occurred as frequently as de novo IHD (1.26 versus 1.22 events/100 patient-years, respectively) and appeared to carry a similar prognosis (relative risk for death, 1.78 [confidence interval, 1.21 to 2.61] for CHF versus 1.50 [1.05 to 2.13] for IHD). The incidence of CHF was considerably higher than that in the Framingham cohort, whereas the incidence of IHD was not, suggesting that renal transplantation might correspond more to a state of "accelerated heart failure" than to "accelerated atherosclerosis." Age, diabetes, gender, BP, and anemia were identified as independent risk factors for de novo CHF, whereas age, diabetes, gender, BP, and rejection were independent risk factors for de novo IHD. Optimal strategies for treatment of BP and anemia in RTR will need to be determined in randomized controlled trials.

Mechanism of angiotensin converting enzyme inhibitor-related anemia in renal transplant recipients

To delineate the pathogenesis of the reduction in hemoglobin occurring in renal transplant patients treated with angiotensin converting enzyme inhibitors (ACEI) and azathioprine (AZA) a controlled, prospective trial of ACEI withdrawal was conducted. The ACEI was replaced by nifedipine or clonidine in 15 kidney transplant patients immunosuppressed with AZA and prednisone (enalapril in 14 and captopril in 1). Before and during 10 to 12 weeks after withdrawal of the ACEI, AZA metabolites, renal function parameters and hematological parameters including erythropoietin and reticulocytes were evaluated. Enalaprilat levels were measured and compared with 15 similar patients matched for transplant function and enalapril dosage immunosuppressed with cyclosporine and prednisone. AZA metabolites did not differ significantly in the presence or absence of the ACEI. Enalaprilat levels also showed no significant difference between the two patient groups treated with AZA or cyclosporine. Hematocrit and hemoglobin increased significantly from 37.5 +/- 6.4 to 39.7 +/- 3.6% (mean +/- SD, P = 0.02) and 12.8 +/- 2.2 to 13.5 +/- 1.2 g/dl, P = 0.04, respectively, 10 to 12 weeks after ACEI treatment had been discontinued. Simultaneously numbers of reticulocytes and erythropoietin concentrations rose significantly after 2, 4 and 10 weeks, with a peak at two weeks (from 14.1 +/- 3.8 to 20.6 +/- 8.0/1000, P < 0.05 and from 14.3 +/- 12.4 to 29.3 +/- 54.5 mU/ml, P < 0.05, respectively). In conclusion, ACEI-related anemia in renal transplant recipients seems to be due to the erythropoietin-lowering effect of this group of drugs. A pharmacokinetic interaction between AZA and enalapril is not likely since plasma enalaprilat levels were independent of the immunosuppressive regimen and AZA metabolite levels were unchanged in the presence and absence of the ACEI. Several mechanisms by which angiotensin converting enzyme blockade may cause a decrease in circulating erythropoietin are discussed.

Enalapril-Associated Anemia in Renal Transplant Recipients Treated for Hypertension

We encountered a renal transplant recipient who developed an unexplained 0.09 decrease in hematocrit value while taking enalapril for hypertension, which reversed when the drug was stopped. This experience, and a previous similar case report, prompted a review of all our 27 transplant patients treated with enalapril. Of these, 10 patients (37%) had developed an otherwise unaccounted for anemia: the pre-enalapril hematocrit value was 0.42 +/- 0.01 and it decreased to the nadir value of 0.33 +/- 0.01 (P less than 0.001) within 12.3 +/- 0.9 weeks after initiation of 9 +/- 2.4 mg of enalapril daily; enalapril was stopped in seven patients and their anemia resolved within 9.1 +/- 0.7 weeks to a final hematocrit value of 0.40 +/- 0.01. The remaining three patients were maintained on enalapril at their physicians' discretion, without further decrease in hematocrit values. No appreciable changes in drug regimens, clinical course, or other laboratory parameters were noted during this period. A causal relationship between enalapril and anemia was suggested by the effect of drug withdrawal and rechallenge on hematocrit in one of the patients. There were no statistically significant differences in baseline clinical and laboratory characteristics between those patients who did (group I) and those who did not (group II) develop enalapril-associated anemia, with the exception of a normal hematocrit value of 0.42 +/- 0.01 in group I versus a lower hematocrit value of 0.36 +/- 0.02 in group II (P less than 0.05). We conclude that enalapril should be considered in the differential diagnosis of anemia following renal transplantation. Susceptibility to this effect might emanate from the immunosuppressed state.