Achieving KDOQI Guidelines for Hematocrit in HIV-Infected Hemodialysis Patients

Abstract

The primary cause of anemia in HIV-infected patients with ESRD is diminished production of erythropoietin. Although most patients respond to recombinant erythropoietin, the response may be blunted in patients with ESRD and concomitant viral or bacterial infections. Previous studies demonstrated a response to erythropoietin by HIV-infected ESRD patients, but hematocrit levels on average were only 27–29%. We were interested in determining if KDOQI guidelines could be met in these patients. Hematocrits and epogen doses of all HIV-positive patients who were undergoing hemodialysis at the Nassau University Medical Center Dialysis Unit between September 2002 and March 2003 were compared to matched controls in our hemodialysis unit. The hematocrit levels in our population were higher than those reported in earlier papers. In our patient population, the mean hematocrit was 37.5, whereas the mean hematocrit levels in the HIV group in previous papers were 27–29%. HIV-infected patients did require higher erythropoietin dosages than controls, but similar doses were used as compared to previous studies. HIV patients on hemodialysis can achieve KDOQI target hematocrits. The difference in route of iron administration and iron stores may explain the higher hematocrit levels in our HIV patient population as compared to previous trials.

Keywords:

• anemia
• erythropoietin
• ESRD
• hemodialysis
• HIV
• KDOQI

INTRODUCTION

Anemia in HIV-infected ESRD patients is frequently multifactorial. It may result from opportunistic infections and drug-induced myelosuppression, but the primary cause of anemia in this population is diminished production of erythropoietin.[1] Anemia in this population is associated with deterioration in cardiac function, decreased cognition and mental acuity, fatigue, and poor exercise tolerance.[2]

Previously, the primary treatment for the anemia of ESRD was red blood cell transfusions and, to a much lesser degree, androgens. However, these approaches failed to correct the anemia and were associated with significant side effects. The development of erythropoietin as a therapeutic option resulted in significant clinical benefits. These included complete correction of the anemia of ESRD, improved quality of life, a significant decrease in the need for ongoing transfusions, and decreased iron burden in patients with iron overload.[3]

Because patients with viral or bacterial infections may have a blunted response to recombinant erythropoietin, there was a concern that HIV-infected ESRD patients may not respond appropriately.[1],[4] A limited number of previous studies demonstrated that HIV-infected patients on hemodialysis do respond to erythropoietin. Their hematocrit (HCT) levels were maintained at similar levels to control patients, albeit at higher erythropoietin dosages. However, in those studies, the mean HCT levels in the HIV group were 27–29%.[5],[6] Given subsequent KDOQI guidelines recommending maintaining HCT levels in the 33–36% range, we determined both the ability to reach these target values in our HIV population on hemodialysis and the dosage of erythropoietin required to reach those values.[7],[8]

MATERIALS AND METHODS

Charts of all the HIV-positive patients who were undergoing hemodialysis at the Nassau University Medical Center Dialysis Unit between September 2002 and March 2003 were reviewed. There were a total of eight patients, all of whom were African American males with a mean age of 49 ± 1.99. For controls, we identified all non-HIV African American males in our hemodialysis unit (10 patients, mean age 53.4 ± 3.41). The exclusion of HIV disease was based on testing for HIV.

Information obtained on each patient included age, gender, race, and monthly HCT, transferrin saturation (TSAT), ferritin, urea reduction rate (URR), cholesterol, and albumin for a three-month period. An average of the three values was calculated for each of the parameters. During this time period, none of the patients received any blood transfusions, and none were hospitalized. There were no changes to the erythropoietin doses during the three-month period, and all patients maintained a stable hematocrit during this time. All patients were treated with conventional dialysis using Baxter CA 210 dialyzers and bicarbonate-based dialysate. There were no significant differences between the HIV patients and the controls in terms of dialysis prescription or duration on dialysis. Target Hematocrit levels were 33–36%. IV iron was used to maintain ferritin levels above 200 ng/mL.

Statistical Methods

Differences between the groups were analyzed using a two-sided unpaired Student's t-test for comparison of hematocrit, transferrin saturation, ferritin, erythropoietin dose, urea reduction rate, cholesterol, and albumin. p < .05 was considered significant. Sigma stat software was used for the analysis.

RESULTS

The responses to erythropoietin in both HIV-infected HD patients and control HD patients are presented in Table 1. There was no significant difference in hematocrit levels or ferritin levels in the HIV population versus controls. Although there was a trend toward higher TSAT levels in the HIV population, it did not reach statistical significance. There was, however, a statistically significant higher erythropoietin dosage used it the HIV population as compared to the control group. In addition, hematocrit levels in our HIV population were higher than those reported in earlier papers. In our patient population, the mean hematocrit was 37.5, whereas the mean hematocrit levels in the HIV group in previous papers were 27–29%. Similar to our patients, HIV-infected patients in previous papers required higher erythropoietin dosages than controls, in similar doses required by our HIV-infected patient population. As seen in Table 2, there were no significant differences in URR, cholesterol, or albumin.

Table 1 Response to erythropoietin in HIV-infected patients on HD

Group	Control (n = 10)	HIV (n = 8)
HCT (%)	37.3 ± 0.605	37.5 ± 1.264
Thrice weekly erythropoietin dose (U/kg body weight)	41.6 ± 12.5	90.2 ± 14.9
TSAT (%)	33.9 ± 5.22	45.9 ± 8.28
Ferritin (ng/mL)	518.8 ± 91.7	607.5 ± 121.2

Values expressed as means ± SEM.

*p < 0.05 compared to control.

Abbreviations: HCT = hematocrit, TSAT = transferrin saturation.

Table 2 Nutritional parameters

Group	Control (10)	HIV (8)
URR (%)	73 ± 1.0	74 ± 2.4
Cholesterol (mg/dL)	142.8 ± 10.7	152.4 ± 13.6
Albumin (g/dL)	3.82 ± 0.122	3.98 ± 0.195

Values expressed as means ± SEM. HIV results are not statistically different from control.

Abbreviation: URR = urea reduction rate.

DISCUSSION

Anemia is a common comorbidity of HIV even in the absence of renal disease.[9],[10] HIV-infected patients with ESRD would seem to be even at a higher risk for anemia and hyporesponsiveness to treatment. However our study demonstrates that HIV patients on hemodialysis who are well-dialyzed can achieve KDOQI target hematocrits. One important caveat is that patients should be well nourished and clinically stable.

The erythropoietin dosages used were statistically higher than controls but similar to those used in previous studies in HIV patients on hemodialysis. In previous studies, the thrice weekly mean erythropoietin dosage used in the HIV population was similar to ours (i.e., 90 units/kg body weight[5]). This suggests that there is some blunting of the response to erythropoietin in this population, which can be overcome by higher doses of the medication.

The hematocrit levels in our population, however, were higher than those reported in earlier papers, where the mean hematocrit levels in the HIV group were 27–29%. One issue concerns the route of administration of iron. Erythropoietin use often causes functional iron deficiency because iron cannot be released fast enough from the stores to meet the increased demands of erythropoietin-stimulated erythropoiesis.[11] IV iron is usually required to reverse this functional iron deficiency. All of the patients in the previous study used oral iron and had mean ferritin levels in the mid-200 range. Our patients were on intravenous iron with mean ferritin levels of approximately 600. The difference in route of iron administration and iron stores may explain the higher hematocrit levels in our HIV patient population as compared to previous trials.

Ideally, management of the HIV infected ESRD patient involves treating underlying illnesses, ensuring adequate nutrition, and normalizing hemoglobin levels through optimizing iron status with intravenous iron and adequate dosing of erythropoietin.

DECLARATION OF INTEREST

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.